Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Metastatic”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2005

Energy balance in patients with advanced NSCLC, metastatic melanoma and metastatic breast cancer receiving chemotherapy--a longitudinal study.

Chemotherapy exerts a variable effect on nutritional status. It is not known whether loss of body fat or fat-free mass (FFM) during chemotherapy relates to diminished dietary intake, failure to meet elevated energy requirements, or to the presence of an acute-phase response. We sought to determine prospective measurements of body mass and composition, resting energy expenditure, energy and protein intake, and C-reactive protein over a course of chemotherapy in 82 patients with advanced cancer. There was a large dropout from the study. Prospective measurements were obtained in 19 patients with non-small-cell lung cancer (NSCLC), 12 with metastatic melanoma and 10 with metastatic breast cancer. There were significant increases in energy intake among patients with metastatic breast cancer, 873 (266-1480) kJ (mean 95% CI; P<0.01), and metastatic melanoma, 2513 (523-4503) kJ (P<0.01). Breast cancer patients gained percentage body fat over the course of treatment, 2.1 (0.8-3.5%). Gain or loss of body fat correlated to mean energy intake throughout chemotherapy in patients with NSCLC (Rs=0.751; P<0.01) and metastatic breast cancer (Rs=0.617; P<0.05). The ability to meet or exceed energy requirements led to gains in body fat among patients with metastatic breast cancer and NSCLC, but did not prevent loss of FFM in these groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.

PURPOSE: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.

Adult↗
PubMed2004

The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer.

INTRODUCTION: Women who smoke have a higher rate of fatal breast cancer than nonsmoking women. An association between smoking and pulmonary metastases from breast cancer has been suggested by epidemiologic studies. STUDY OBJECTIVES: To examine the relationship between exposure to cigarette smoke and pulmonary metastasis in a murine model of metastatic mammary cancer. STUDY DESIGN: Prospective, randomized study. SETTING: Animal research laboratory. EXPERIMENTAL SUBJECTS: Female sexually mature BALB/cAnN mice. INTERVENTIONS: Mice were randomly divided into experimental and control groups. Experimental animals were exposed to cigarette smoke in specialized exposure chambers, at concentrations chosen to approximate active cigarette smoking. Control animals were exposed to filtered air. One week after the initiation of exposures, mouse mammary tumor cells (tumor cell line 4526) were injected into the tail veins of experimental animals at one of three concentrations (50,000, 100,000, or 150,000 cells per 100 micro L). Three weeks later, the mice were killed, and pulmonary metastases were counted and measured. RESULTS: The mean metastatic burden in the lungs was consistently greater for smoke-exposed animals at each concentration of cells injected (at 50,000 cells per 100 micro L, 9.8 vs 4.8 micro m(3), respectively [p < 0.01]; at 100,000 cells per 100 micro L, 34.5 vs 17.4 micro m(3), respectively [p < 0.10]; and at 150,000 cells per 100 micro L, 54.0 vs 31.5 micro m(3), respectively [p < 0.05]). This was largely attributable to a significant increase in the number of metastatic nodules per animal (at 50,000 cells per 100 micro L, 8.7 vs 4.8, respectively [p < 0.001]; at 100,000 cells per 100 micro L, 24.3 vs 14.0, respectively [p > 0.10]; and at 150,000 cells per 100 micro L, 42.0 vs 20.1, respectively [p < 0.02]) rather than to a change in nodule size. CONCLUSIONS: Cigarette smoke exposure is associated with an increase in the total pulmonary metastatic burden in this murine model of metastatic mammary cell cancer. This study provides experimental support for an adverse effect of smoking on the metastatic process and suggests a possible mechanism for smokers' increased breast cancer mortality.

Animals↗
PubMed1991

[Selection of highly metastatic lines from streptozotocin-induced mouse renal adenocarcinoma and their in vivo metastatic or in vitro invasive potential].

We selected highly metastatic lines from mouse renal adenocarcinoma (STZ-RCC) chemically induced with streptozotocin. At eight weeks after an intrasplenic injections (IS injection) of original STZ-RCC, this procedure yielded metastatic foci in the liver, which we transplanted serially in syngeneic mice (STZ-HM1). STZ-HM1 was then injected into the spleen of a syngeneic mouse, which provided a source for further cycles of hepatic metastasis selection. Three cycles of selection for hepatic metastasis yielded a high hepatic metastasis line (STZ-HM3). Intravenous injection of the parent line (original STZ-RCC) yielded metastatic foci in the lung eight weeks later, which we also transplanted serially in syngeneic mice (STZ-PM1). The repeated IS injection of the cells was clearly responsible for the increase in the frequency of hepatic metastasis and the number of its nodules. In particular, STZ-HM3 was revealed to have more metastatic nodules in the liver ranging from 293 to 432 (median; 368) in all five mice at eight weeks after IS injection. STZ-PM1 had a significantly higher rate of pulmonary metastasis and more pulmonary metastatic nodules after intravenous injection than the parent line. These results confirm that the parent line, STZ-RCC, has a heterogeneity in the metastatic phenotype. In vitro invasion assay for STZ-RCC, STZ-HM1, -HM2 and -HM3 demonstrated that in vitro invasive potential was paralleled with in vivo hepatic metastasis potential. The result suggests that the invasion potential revealed by in vitro invasion assay is important in metastasis formation.

Animals↗
PubMed2001

Identification of metastasis associated gene G3BP by differential display in human cancer cell sublines with different metastatic potentials G3BP as highly expressed in non-metastatic.

OBJECTIVE: To investigate genes involved in cancer metastasis, mRNA differential display was used to compare the levels of gene expression in two cell sublines derived from human giant cell carcinoma of lung (PG) which had different metastatic potentials. METHODS: Using in vivo tumorigenicity and a spontaneous metastasis assay in nude mice, two sublines (BE1, LH7) from human giant cell carcinoma of lung (PG) with different metastatic potentials were isolated and characterized. mRNA differential display was used to compare the levels of gene expression between them and the obtained results were confirmed by Northern hybridization. RESULTS: One differentially expressed band was nearly identical (99% homology) to Ras-GTPase-Activating protein SH3 domain binding protein (G3BP). G3BP displayed a strong expression in LH7 (non-metastatic in recipient nude mice) and a very weak expression in BE1 (100% metastatic frequency). The same different expression level of G3BP was detected in Northern hybridization with another panel of cell sublines with different metastatic potentials (established in our lab) derived from human prostate carcinoma cell line PC-3M. CONCLUSION: Our results indicate that G3BP was implicated in cancer metastasis because of its differential expressions in the two panels of cell sublines with different metastatic potentials.

Animals↗
PubMed2003

[Study on differentially expressed molecules influencing the metastatic potential between highly and poorly metastatic human lung giant cell carcinoma].

OBJECTIVE: To study the metastasis-associated molecules differentially expressed in highly and poorly metastatic sublines and the mechanism of metastasis in lung giant cell carcinoma. METHODS: Highly and poorly metastatic sublines (PLA801D and PLA801C)were used as metastasis model. Cell motility and invasion assay in vitro were first compared between the two sublines. Then, gelatin zymography analysis was used to determine the MMP-2 and MMP-9 activity. The protein expression level of secreted MMP-2, MMP-9, TIMP-1, TIMP-2 and intracellular expression level of p53, p16, PCNA, CD44(V6) isomeride, E-cadherin, CK18, nm23-H1 as well as the mRNA expression level of MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF were compared through Western blot. Semi-quantitative RT-PCR analysis was used to determine the intracellular mRNA expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and VEGF. RESULTS: The in vitro cell invasion potential of highly metastatic subline PLA801D was significantly higher than that of poorly metastatic subline PLA801C by about 4 folds, while the cell motility potential was similar. The secreted MMP-2 activity was notably higher in PLA801D, which was initiated by the higher expression of MMP-2 at protein and mRNA level. In addition, the expression level of p53, PCNA, CK18 protein and VEGF mRNA were significantly higher, while the expression level of p16, E-cadherin and nm23-H1 protein were significantly lower in PLA801D. Some molecules such as MMP-9, TIMP-1, TIMP-2, CD44(V6) isomeride, which had been reported to be associated with tumor metastasis, were not observed to change significantly between the two sublines. CONCLUSION: There are significant differences in metastatic potential and phenotypes between highly and poorly metastatic sublines of lung giant cell carcinoma. Some differentially expressed molecules might be playing roles in promoting or inhibiting metastasis of lung giant cell carcinoma, which may be useful to elucidate the mechanism of metastasis.

Carcinoma, Giant Cell↗
PubMedDate not supplied

Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor.

The highly (ASML) and non metastatic (AS) variants of the rat tumor BSp73 were compared with respect to cell surface carbohydrate proteins. Fluorescence labelling with lectins (ConA, MPA, PNA, SBA, UEA-I, WGA) revealed a differentiated carbohydrate pattern at the cell surface of these cell lines. The highly metastatic variant was significantly more glycosylated with respect to galactosyl, mannosyl and N-acetylgalactosylamine residues; fucosyl residues were exclusively expressed in the metastatic variant. Examination of isolated plasma membrane fractions showed quantitative differences with respect to glycosylated proteins separated on polyacrylamide gels. A 30 kDa glycoprotein (GP30-ASML) dominant in the metastatic variant was further characterized. Various detergents (CHAPS, Nonidet, SDS, Triton X-100) and urea extracted it exclusively from the highly metastatic variant. GP30-ASML is a predominantly O-glycosylated single polypeptide chain with terminal N-acetylgalactosamine and galactosyl residues; its molecular weight determined by SDS-PAGE is 30 kDa and its isoelectric point is 7.8. Immunofluorescence localization experiments with monoclonal antibodies specific for GP30-ASML and polyclonal antibodies raised against GP30-ASML showed this protein at the cell surface and in the lysosomal compartment of both cell lines; exclusively in the non metastatic variant it was also found in the nuclear membrane. The function of this protein is still unknown.

Adenocarcinoma↗
PubMed1988

Growth of rat mammary adenocarcinoma cells in semisolid clonogenic medium not correlated with spontaneous metastatic behavior: heterogeneity in the metastatic, antigenic, enzymatic, and drug sensitivity properties of cells from different sized colonies.

Using rat 13762NF mammary tumor cell clones of varying spontaneous metastatic potentials and biochemical properties and known phenotypic stabilities we studied the relationship between cell colony growth in a clonogenic assay and the biological and biochemical properties of cells derived from different cell colonies. The spontaneous metastatic potential of in vivo or in vitro grown 13762NF tumor cells was not related to their in vitro cloning efficiencies; cells of both low and high metastatic potential formed colonies of various sizes and shapes during 14 days of growth in 0.3% or 0.6% semisolid agarose. A highly metastatic cell clone of relatively low growth potential in agarose was examined further. Individual tumor cell colonies derived from this cell clone were removed from agarose and their properties determined. Cells from small (less than 100-microns-diameter) or large (greater than 500-microns-diameter) agarose colonies had similar self-renewal capacities in agarose and formed variously sized cell colonies when replated in agarose medium. Metastatic potential, drug sensitivity parameters, and expression of a high Mr mucin-like glycoprotein antigen and type IV collagenolytic activity known to be associated with spontaneous metastasis of 13762NF tumor cells were dissimilar in cells from different colonies, and these characteristics were independent of original tumor cell colony size in agarose. In contrast, the expression of cell surface proteins of Mr less than 300,000 were similar among cells derived from different agarose colonies. The data indicate that heterogeneity exists in the ability of 13762NF adenocarcinoma cells of different biochemical and metastatic potentials and drug sensitivities to grow in semisolid agarose. In addition, the cells that grow in agarose to form detectable colonies (greater than 50 cells) are not necessarily those with a high potential of metastasizing spontaneously to distant sites.

Adenocarcinoma↗
PubMed1986

Metastatic potential and spontaneous mutation rates: studies with two murine cell lines and their recently induced metastatic variants.

To investigate the hypothesis that increased malignant potential correlates with increased genetic instability, we measured spontaneous mutation rates for the production of ouabain-resistant mutants in two benign (nonmetastatic) murine cell lines and their recently induced metastatic variants. Metastatic variants of the NIH 3T3 and CBA SP-1 cells were induced by transfection with the h-ras oncogene. Metastatic variants were also induced from the CBA SP-1 cell line by treatment with either 2'-deoxy-5-azacytidine or hydroxyurea. Mutation rates for the parent NIH 3T3 cells and their metastatic variants were less than 3 X 10(-8) variants per cell per generation, with no significant differences between them. Rates for the CBA SP-1 line and its variants ranged from 9 X 10(-9) to 8 X 10(-8) variants per cell generation, again without statistically significant differences. We conclude that in the cell lines studied the rate of spontaneous mutation for ouabain resistance was unrelated to the acquisition of the metastatic phenotype. This conclusion was based on the view that the generation of ouabain-resistant mutants is a reflection of the overall stability of the genome. Since the spontaneous mutation rate for ouabain resistance was unchanged in cells that had recently acquired the ability to metastasize, other genetic or epigenetic events were probably responsible for progression to the malignant (metastatic) phenotype.

Animals↗
PubMed1997

Comparison of DNA gains and losses in primary renal clear cell carcinomas and metastatic sites: importance of 1q and 3p copy number changes in metastatic events.

Archival material from primary and metastatic renal clear cell carcinomas of 25 patients was studied by comparative genomic hybridization. Copy number changes of entire chromosomes or chromosomal subregions were detected in 22 primary and 21 metastatic tumors. Copy number changes affected the following chromosomes in at least 20% of the 25 primary tumors (minimal common region given in parentheses): gains were noted for chromosomes 1 (1q21-->q23), 5 (5q31-->q34), 7 (7p), 8 (8q), 16 (16p), 17 (17q12-->qter), 19, and 22 (22q12-->qter); losses were revealed for chromosomes 3 (3p21-->pter), 8 (8p23-->pter), 14(14q21-->qter), and Y. The same chromosomal regions that were involved in primary renal clear cell carcinomas were also found in the respective metastatic tumors but with strikingly different frequencies for a few regions. Metastatic tumors showed a significantly higher frequency of complete or partial gains of the long arm of chromosome 1, in particular at 1q21-->q23 than primary tumors (16 cases versus 6 cases; P < 0.005). These data suggest a correlation of metastatic events in renal clear cell carcinomas with an increase in the copy number of genes located at 1q, in particular at 1q21-->q23. In contrast, the entire or partial loss of the short arm of chromosome 3 was significantly less frequent in metastatic tumors (8 cases versus 15 cases; P < 0.025). The validity of 1q and 3p copy number changes detected by comparative genomic hybridization was confirmed by interphase cytogenetics with region-specific yeast artificial chromosomes to paraffin-embedded tumor tissue sections.

Adenocarcinoma, Clear Cell↗
PubMed1983

Metastatic uveal melanoma. Hepatic cell-surface enzymes, isoenzymes, and serum sialic acid levels in early metastatic disease.

Serum hepatic cell-surface enzymes, isoenzymes, and sialic acid levels may be useful adjuncts in detecting early metastatic disease and in evaluating the tumor burden of patients with uveal melanoma. Hepatic cell-surface enzyme concentrations were elevated in the serum of ten patients with uveal melanoma and liver metastasis and in five patients with other hepatobiliary disorders and in 75 control patients. Five patients in the metastatic group (50%) had serum gamma-glutamyl transpeptidase and 5'-nucleotide phosphodiesterase (5-NPD) bands known to be associated with either primary hepatic carcinoma or carcinoma metastatic to the liver. One patient with uveal melanoma without known metastasis had a positive 5-NPD pattern; metastatic disease was subsequently proved. Higher levels of sialic acid were found in the serum of patients with uveal melanoma and metastatic disease (4 mumole/mL) than in controls (2.4 mumole/mL).

Adult↗
PubMed2002

Reduced sialidase expression in highly metastatic variants of mouse colon adenocarcinoma 26 and retardation of their metastatic ability by sialidase overexpression.

Sialidase expression levels are inversely correlated with the metastatic potential of mouse colon adenocarcinoma 26 sublines, as assessed by activity assays and RT-PCR, irrespective of total and cell surface sialic acid contents. Compared with low metastatic NL4 and NL44 cell lines, the highly metastatic NL17 and NL22 cells exhibit low expression of sialidases, accompanied with higher levels of sialylLe(x) and GM3. To investigate whether these properties of NL17 cells can be altered by sialidase overexpression, we transfected a cytosolic sialidase gene into NL17 cells. The result was markedly inhibited lung metastasis, invasion and cell motility with a concomitant decrease in sialylLe(x) and GM3 levels, in line with the case of spontaneously low metastatic sublines having relatively high endogenous sialidase levels, implying that sialidase level is a determining factor affecting metastatic ability. Treatment of the cells with antibodies against sialylLe(x) and GM3 affected cell adhesion and/or cell motility, providing evidence that desialylation of these molecules, as targets of sialidase, is involved in the suppression of metastasis.

Adenocarcinoma↗
PubMed1979

Ganglioside patterns of metastatic and non-metastatic transplantable hepatocellular carcinomas of the rat.

In previous investigations, we correlated levels of sialic acid, gangliosides, and ganglioside glycosyltransferases with tumorigenesis over a 24-week continuum of growth of hepatocellular neoplasms of the rat induced by the carcinogen N-2-fluorenylacetamide. However, metastatic tumors developed only rarely and were not analyzed. To investigate surface changes associated with metastasis, well-differentiated and poorly differentiated hepatocellular carcinomas were transplanted to syngeneic recipient rats. From those, several metastatic and nonmetastatic isolates were obtained and compared. Both total and ganglioside sialic acid amounts in transplantable hepatomas were elevated above control liver values but were significantly lower for metastatic lines than for nonmetastatic lines. The nonmetastatic lines were characterized by ganglioside patterns depleted in the precursor ganglioside GM3 (sialic acid-galactose-glucose-ceramide) and elevated in the products of the monosialoganglioside pathway. In contrast, metastatic isolates exhibited a restoration of GM3 and nearer normal amounts of other gangliosides. The findings point to differences in sialic acid-containing glycolipids, comparing metastatic and nonmetastatic hepatocellular carcinomas, and further extend the concept that ganglioside alterations do not cause tumorigenesis but are the end result of a cascade of events which apparently continue beyond the onset of metastasis.

2-Acetylaminofluorene↗
PubMedDate not supplied

In vitro modulation of the metastatic phenotype. I. Analysis of differentiation forms of the B16 melanoma expressing Met-72 determinants and metastatic activity.

In vitro cultures of a highly metastatic B16 melanoma clone (BL6-10) were found to undergo dramatic changes in morphology and differentiation upon transfer to another culture medium. Specifically, BL6-10 melanoma cells which had been originally selected and adapted for growth in Eagles' Hanks' amino acid supplemented media with 10 per cent newborn calf serum were amelanotic and epitheliod in shape. When these cells were shifted into Dulbecco's modified Eagles medium with 10 per cent fetal calf serum, they became highly melanotic and of spindle/dendritic morphology within 4 days of culture. These morphological changes as well as other parameters were all characteristic of established criteria of melanoma differentiation. Alterations in the differentiation state of our highly metastatic variant, BL6-10, did not result in any change in tumorigenicity but did have profound effects on metastatic potential. All of the morphological and functional characteristics of the differentiated melanoma were found to be reversible by re-plating the cells in their original growth medium and 4 days of in vitro growth. These studies have allowed us to follow and more firmly establish Met-72 antigen expression as a surface marker for metastatic cells of the B16 melanoma, and have provided direct experimental evidence that the less differentiated, Met-72 positive melanoma form is the dominant cell type capable of metastatic potential.

Animals↗
PubMedDate not supplied

Studies on the expression of H-2 antigens in non-metastatic and highly metastatic Friend erythroleukemia cells: correlation with the in vivo behaviour of tumor cells.

The levels of expression of histocompatibility antigens on the cell membrane and their gene expression in non-metastatic and in highly metastatic Friend leukemia cells (FLC) were measured and the levels of expression of these antigens were correlated with the different in vivo behaviour of the tumor cells. Highly metastatic in vivo passaged FLC (either interferon-sensitive 745 or interferon alpha/beta-resistant 3Cl-8 cells) expressed higher levels of class I H-2K and H-2D antigens on their cell membrane with respect to the non-metastatic in vitro passaged counterparts. The increased expression of H-2 class I antigens was associated with an increased transcription of H-2K and H-2D genes. As both in vitro and in vivo passaged FLC have been shown to be resistant in vitro to the natural killer (NK) cell activity, we tried to correlate the levels of expression of histocompatibility antigens with the in vivo clearance of [125I]UDR-labeled FLC. However, no correlation was found between the levels of expression of H-2 antigens and the in vivo clearance of tumor cells. In fact, in vivo passaged FLC (tested either after 1 or after 15 in vitro passages) expressed virtually identical levels of H-2 antigens; however, the freshly explanted in vivo passaged FLC exhibited markedly lower levels of clearance from the lung, spleen and liver (when injected i.v. in DBA/2 mice) with respect to the corresponding FLC cultivated for several passages in vitro. Pretreatment of in vitro passaged 745 FLC with either interferon alpha/beta or interferon gamma resulted in the acquisition of some metastatic potential of FLC to the liver when interferon-treated FLC were subsequently injected i.v. in DBA/2 mice; such in vitro treatments resulted in a 2-3-fold increase in the expression of H-2K antigens versus the control untreated FLC. We suggest that such increases could represent some advantages for the homing properties of tumor cells and/or for the tumor progression, by mechanisms different from the resistance to the NK cells.

Animals↗
PubMed2000

Treatment modalities for metastatic bone tumors and associated issues: focusing on surgical indications and techniques for metastatic lesions in limb bones.

Metastatic bone tumors are traditionally the most commonly encountered form of malignant bone tumor. In recent years, the prevalence of metastatic bone tumors has shown a tendency of further increase, due to advances in cancer treatments that prolong survival. Accompanying this increase, the chances that orthopedic surgeons will encounter these tumors and the need for surgical treatment are increasing. Metastatic bone tumor usually constitutes only part of the metastatic lesions. Although local control at the bone metastatic site alone may have little effect on the total curability, the quality of life (QOL) of the patient cannot be ensured if local control is ignored. Therefore it is important to achieve local control by interdisciplinary treatments aiming at reduced surgery and at functional conservation.

Adolescent↗
PubMed1996

Expression of CD44 splice variants in metastatic and non-metastatic mouse tumour cell lines.

Different splice variants of the CD44 cell-surface molecule have been linked to metastasis formation in several animal and human cancers. We have used metastatic CSML-100 and non-metastatic CSML-0 mouse adenocarcinoma cell lines to determine whether variant CD44 molecules could be implicated in the different behaviour of these cells. Two CD44 splice variants containing exons v7-v10 and v8-v10 were detected in the non-metastatic CSML-0. Two other mouse cell lines, the normal mammary gland NMuMG and the mammary pre-neoplastic CL-S1 were also found to express these exons. A short (hematopoietic) CD44 isoform was expressed in the metastatic CSML-100 and three other mouse mammary tumour cell lines. Overexpression of v7-v10 and v8-v10 CD44 variants in CSML 100 cells did not decrease their metastatic potential.

Alternative Splicing↗
PubMed2003

Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype.

In the present study, we examined the autocrine/paracrine role of IL-8 in melanoma growth and metastasis by analyzing the expression and functional significance of IL-8 receptors, CXCR1 and CXCR2 in human malignant melanoma cells with different metastatic potential. CXCR1 and CXCR2 mRNA and protein levels were analyzed by reverse trannscriptase-based polymerase chain reaction, immunohistochemistry, immunoprecipitation, flow cytometry and ligand binding assay in melanoma cells in vitro and xenografted in nude mice. Melanoma cells constitutively expressed CXCR1 and CXCR2 mRNA and protein. Highly metastatic A375SM cells expressed higher levels of CXCR1 and CXCR2 mRNA and protein in vitro and in vivo as compared to low metastatic A375P and non-metastatic SBC-2 melanoma cells. Treatment of SBC-2 and A375P cells with exogenously added recombinant IL-8 significantly enhanced their proliferation and invasive potential. Further neutralizing antibodies to CXCR1 and CXCR2 inhibited proliferation and invasive potential of unstimulated and IL-8-stimulated A375P cells. In summary, the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells.

Animals↗