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PubMed1999

CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma.

BACKGROUND: The expression of the CD44 gene is markedly changed in many neoplastic tissues. The identification of tumor-specific CD44 expression patterns may aid tumor diagnosis. METHODS AND RESULTS: The transcription and translation of the CD44 gene were analyzed by reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and by immunohistochemistry. Samples were obtained from 24 normal and 24 neoplastic or malignant human cervical tissues. Southern blot hybridization analysis of RT-PCR products revealed an increase in the size and number of CD44 standard and variant transcripts in malignant cervical tissues compared with corresponding normal tissues. Misprocessing of mRNA was indicated in cervical carcinoma cells by the retention of intronic sequences. Multiple CD44 mRNA and protein isoforms were present throughout carcinoma tissues, whereas localization was restricted to the basal epithelium in normal cervical tissue. Analysis of desquamated cervical cells from cases of cervical intraepithelial neoplasia stages I-III showed progressively deranged patterns of CD44 expression, with more alterations being detected in the more advanced stages. CONCLUSIONS: Marked alterations in CD44 expression occur in cervical tissues during progression to malignancy. CD44 expression analysis could aid the early diagnosis of cervical malignancy using minimally invasive methods.

Antigens, Neoplasm↗
PubMed1997

CD44 variant expression and estrogen receptor status in breast cancer.

To understand the relationship between CD44 gene expression and an established variable associated with aggressive behaviour in human breast cancer, we have studied a panel of 6 breast cell lines and 40 breast tumors selected primarily on the basis of estrogen receptor (ER) status. CD44 (standard form) mRNA was assessed by semi-quantitative RT-PCR, and CD44 variants incorporating exon v7 or v10 were studied by RT-PCR and Southern blot. While CD44 expression was not influenced by estrogen in ER+ve MCF-7 cells. CD44s expression was slightly higher (up to 2 fold) in ER-ve cells but there was a marked decrease in the range of CD44 variants incorporating exons v7 or v10. In microdissected tumors, the levels of CD44s showed no correlation with ER status but the pattern of expression of larger forms of CD44 incorporating variant exons v7 and v10 was significantly different (p = 0.005 and p = 0.015, respectively) between ER+ve and ER-ve tumors, reflecting the pattern seen in the cell lines. These findings suggest that the profile of CD44 expression in breast cancer may reflect cellular differentiation as indicated by the ER phenotype. The influence of these differences in CD44 expression on the increased metastatic potential of ER negative breast cancer remains to be determined.

Breast Neoplasms↗
PubMed1999

Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan.

The adhesion of tumour cells to the hyaluronan (HA) pericellular coat of mesothelial cells is an important step in the peritoneal spread of ovarian cancer. Previously, we have shown that the cell surface molecule CD44 is involved in this process. Paradoxically, the degree of adhesion does not appear to be related to the amount of CD44 expressed. In order to explain this observation we have examined the in vitro adhesion to HA of four high CD44-expressing ovarian cancer lines in relation to their CD44 spliced variant content and the CD44 glycosylation. Adhesion was measured in multiwell plates coated with different concentrations of HA in order to determine both the avidity and the maximum adhesion. Two lines had high adhesion and two lines had low adhesion. The avidity for HA was different for each line, but in all cases this could be totally blocked by treatment with an anti-CD44 antibody. The standard form of CD44 was the major species detected by RT/PCR in all lines and spliced variants were present in low amounts. Neuraminidase treatment increased the adhesion of the 'low-adhesion' lines at all HA coating concentrations; but only substantially increased the adhesion of the 'high-adhesion' lines at the lower HA coating concentrations. Tunicamycin treatment decreased the adhesion of the 'high-adhesion lines' at all HA coating concentrations and only substantially decreased the adhesion of one of the 'low-adhesion' lines when the plates were coated with a low concentration of HA. The adhesion of the remaining 'low-adhesion' line was slightly increased after tunicamycin treatment. It is concluded that glycosylation and not spliced variant content of CD44 affects the adhesive properties of ovarian tumour cells. This conclusion may have important consequences for developing new therapies in ovarian cancer.

Carcinoma, Endometrioid↗
PubMed1995

Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer.

The surface glycoprotein CD44 is widely distributed in different tissues. In contrast to healthy tissue, tumour samples show a more complex pattern of CD44 expression, indicating a loss of splice control. Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status. We evaluated the surface expression of CD44 isoforms in 22 ovarian cancer patients by means of immunohistochemistry. Additionally, we investigated 134 serological samples of these patients for the occurrence of CD44 isoform expression. For CD44 standard, CD44v5 and CF44v6 mean serum levels in patients with clinically detectable or non-detectable ovarian cancer were 422.4 +/- 143.8 ng ml-1 and 547.4 +/- 148.2 ng ml-1, 12.3 +/- 7.9 ng ml-1 and 21.9 +/- 12.2 ng ml-1 and 105.5 +/- 37.9 ng ml-1 and 144.9 +/- 50.9 ng ml-1 respectively (P-values not significant). CD44 surface proteins containing epitopes encoded by splice variants CD44v5, CD44v6 and CD44v7-8 were immunohistochemically detected in 9% (n = 2), 13% (n = 3) and 4% (n = 1) of the 22 tumour samples respectively. In the present study we showed that in ovarian cancer CD44 isoforms CD44v5 and CD44v6 are expressed in very low amounts by the tumours. In accordance with this, we found that the presence of tumour is not associated with higher serum levels of CD44standard, CD44v5 and CD44v6 in preoperative serum samples in ovarian cancer patients.

Adult↗
PubMed2002

CD44 is exposed to the extracellular matrix at invasive sites in basal cell carcinomas.

We have previously shown, by light microscopy, that the level of expression of CD44 (pan-CD44, CD44v3, CD44v5, and CD44v6) in human basal cell carcinomas is related to growth pattern and invasiveness (Br J Dermatol 1099;140:17-25). We have now studied the fine distribution of these CD44 isoforms in the same tumors using immunoelectron microscopy. Despite the strong differences in the level of expression in tumor areas with different growth patterns, CD44 was consistently found almost exclusively at intercellular surfaces, with a very strong predilection for widened intercellular pouches, ie, identical to the distribution in the normal epidermis. This prevalent distribution corroborates a role for CD44 in maintaining hyaluronan-filled spaces (J Histochem Cytochem 1998;46:241-248). However, the correlation between the presence of CD44 and the presence of such pouches was not absolute, indicating that other factors are involved as well. In contrast to the prevailing literature, we also found a weak but distinct labeling of cell surfaces facing the extracellular matrix. Interestingly, this appeared significantly elevated in the thinnest, most irregular, and usually most peripheral tumor cell strands, where it was associated with tumor cell protrusions and absence of a basal lamina. Thus, the CD44(+) protrusions were in direct contact with the extracellular matrix and apparently represented sites of invasion. The mechanisms that may contribute to a role of CD44 at these sites include binding of extracellular matrix components (notably hyaluronan) and several biologically active factors such as hepatocyte growth factor/scatter factor and matrix metalloproteinase 9.

Basal Cell Carcinoma↗
PubMed2000

Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia.

The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification. A total of 120 papillary urothelial pTa and pT1 tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression in stage with CK20 and CD44 immunoreactivity were assessed. WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as well as in the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior in patients with papillary urothelial pTa and pT1 neoplasms.

Adult↗
PubMed2002

Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line.

Over-expression of the adhesion molecule CD44 and its splice variants, especially CD44v6, is associated with poor prognosis and metastasis. We aimed at regulating the expression of CD44 in the highly metastatic human colon cancer cell line HM7 and thereby affecting its metastatic ability. HM7 cells show constitutive expression of CD44 standard and variants isoforms, which were significantly down-regulated by treatment with butyrate. Butyrate significantly inhibited transcription of the CD44 gene and abolished epidermal growth factor-mediated up-regulation of the reporter gene luciferase subcloned upstream to the CD44 promoter (-1.1 kb) and transfected to HM7 cells. Nuclear proteins from butyrate-treated cells bound to an epidermal growth factor receptor element motif present in the CD44 promoter. Epidermal growth factor receptor element-site directed mutations eliminated the inducibility of the luciferase reporter gene and did not allowed binding of nuclear proteins harvested from butyrate-treated cells. Butyrate induced CD44 gene repression by specifically interacting with an epidermal growth factor receptor element nuclear transcriptional factor. This interaction affects CD44 transcriptional activity vis-à-vis in vivo metastatic ability of HM7 cells. These results provide additional insight into the anticarcinogenic properties of butyrate.

Butyrates↗
PubMed1999

Expression of CD44 by rhabdomyosarcoma: a new prognostic marker?

The expression pattern of CD44 standard and variant isoforms are prognostically significant in a number of malignancies. The aim of this study was to evaluate the role of the standard isoform of CD44 in predicting the clinical behaviour of rhabdomyosarcoma. Immunohistochemical analysis of CD44 was undertaken using a panel of antibodies recognizing the three core domains of the CD44 molecule. Labelling was repeated in triplicate and reported blind with respect to histological type and outcome. Tumours were characterized as positive in more than 60% of tumour cells labelled and negative if less than 40% of tumour cells labelled. Tumours with 40-60% of tumour cells labelling were considered indeterminate. Eleven of 20 favourable histology tumours were positive for CD44 compared with one of seven unfavourable tumours (P = 0.07). Eleven of 12 patients with CD44-positive tumours are alive in first remission compared with five of 15 CD44-negative tumours (P = 0.001). Expression of CD44 correlates directly with prognosis; however, larger studies are required so that multivariate analysis can be undertaken.

Adolescent↗
PubMed2006

Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10.

Invasive tumour cells, such as gliomas, frequently express EGF (epidermal growth factor) receptor at a high level and they exhibit enhanced cell migration in response to EGF. We reported previously that tumour cell migration is associated with ectodomain cleavage of CD44, the major adhesion molecule that is implicated in tumour invasion and metastasis, and that the cleavage is enhanced by ligation of CD44. In the present study, we show that EGF promotes CD44 cleavage and CD44-dependent cell migration. Introduction of a dominant-negative mutant of the small GTPase Rac1 or depletion of Rac1 by RNAi (RNA interference) abrogated CD44 cleavage induced by EGF. Treatment with PD98059, an inhibitor for MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase), also suppressed the CD44 cleavage. Furthermore, RNAi studies showed that EGF induced ADAM10 (a disintegrin and metalloproteinase 10)-dependent CD44 cleavage and cell migration. These results indicate that EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion.

ADAM Proteins↗
PubMed2003

Hyaluronan, CD44 and versican in epidermal keratinocyte tumours.

BACKGROUND: The high molecular weight polysaccharide hyaluronan is a major component of the extracellular matrix between the vital cells of human skin epidermis. The levels of hyaluronan, and those of the hyaluronan receptor CD44 and the hyaluronan binding proteoglycan versican, correlate with the aggressiveness of different human carcinomas of epithelial origin. OBJECTIVES: To study skin keratinocyte tumours for the expression of hyaluronan, the hyaluronan receptor CD44 and the hyaluronan binding proteoglycan versican. METHODS: Paraffin-embedded sections of 114 basal cell carcinomas (BCC), 31 in situ carcinomas (ISC) and 35 squamous cell carcinomas (SCC) were stained with a hyaluronan specific probe, biotinylated hyaluronan binding complex, and with monoclonal antibodies against CD44 and versican. RESULTS: Compared with normal epidermis, ISC and well differentiated SCCs showed an enhanced hyaluronan signal on carcinoma cells while CD44 expression level resembled that of normal skin. Less differentiated SCCs showed reduced and irregular expression of both hyaluronan and CD44 on carcinoma cells. In BCCs, hyaluronan and CD44 signals were absent or very low on the surface of carcinoma cells. However, hyaluronan was frequently present on BCC cell nuclei, a feature completely absent in ISC, SCC and normal epidermis. An accumulation of hyaluronan in the connective tissue stroma around the tumour was more frequent in SCCs than BCCs. Versican staining was positive around hair follicles and dermal blood vessels of normal skin. Peritumoral versican signal was present in a part of the BCCs but not in other tumours. CONCLUSIONS: The completely different hyaluronan and CD44 expression patterns in BCC and SCC probably reflect the different origins of the tumours, with BCC an undifferentiated keratinocyte and SCC a keratinocyte at an early stage in the differentiation pathway. The difference in hyaluronan and CD44 expression between these tumours may also contribute to the difference in their capacity to metastasize.

Carcinoma↗
PubMed1998

Evidence for differences in the mechanisms by which antibodies against CD44 promote adhesion of erythroid and granulopoietic progenitors to marrow stromal cells.

Adhesive interactions between haemopoietic progenitor cells and stromal elements involve a number of different molecules, some of which may be progenitor- lineage- and stage-specific. CD44 is one such molecule, although little is known about the mechanism(s) by which it is involved. In this study, several anti-CD44 monoclonal antibodies (mAb) increased the adherence of clonogenic cells, without affecting the total number of types of progenitors recoverable from the adhesion cultures. All of these mAb recognized epitopes on the globular head of CD44. In contrast, two mAb that recognized other regions of CD44 reduced progenitor adhesion to stroma. The mechanism by which one of the anti-CD44 mAb (L178) enhanced progenitor adhesion did not involve CD44-crosslinking, and was independent of VLA-4-, VLA-5- or LFA-1-mediated interactions, Ca or Mg cations, or accessory cells. In addition, CD44 expression on both progenitors and stromal cells contributed to L178-enhanced progenitor adhesion. Baseline adherence of erythroid progenitors to stroma required tyrosine kinase activity, whereas that of granulopoietic progenitors did not. However, the increase in adhesion did require tyrosine kinase activation. Additional experiments suggested that enhanced adhesion of CFU-GM to stroma may also be adenylate cyclase-dependent. Taken together, the present studies indicate both similarities and differences in the mechanisms of CD44-mediated adhesion of erythroid and granulopoietic progenitors to stromal cells.

Adenylyl Cyclases↗
PubMed1998

Influence of ischaemia-reperfusion injury on CD44 expression in rat small intestine.

BACKGROUND: CD44 is an adhesion molecule expressed by neutrophils and lymphocytes which is involved in cell-cell and cell-matrix binding. In this study, the effect of ischaemia-reperfusion injury on CD44 messenger RNA (mRNA) and cell surface immunohistochemical expression of CD44 in the rat small intestine was evaluated. METHODS: Wistar rats (n=16) were randomized to either serve as controls (sham surgery) or to be subjected to a standardized ischaemia-reperfusion injury (suprarenal aorta occluded for 1 h followed by 1 h of reperfusion). Standardized segments of jejunum were harvested after ischaemia-reperfusion injury (ischaemic and reperfused samples) to measure the mucosal protein and DNA content, mRNA expression of CD44 and the immunohistochemical expression of CD44. RESULTS: Reperfusion significantly damaged the jejunal mucosa, e.g. mucosal protein content was lower after reperfusion compared with that in the control group (z=-2.31, P=0.02) and the ischaemic samples (z=-2.52, P=001). The expression of cell surface CD44 protein was also significantly decreased after ischaemic injury (z=-1.99, P=0.04); this coincided with a decrease in the amount of cytoplasmic CD44 mRNA within isolated enterocytes (z=-2.31, P=0.02). CONCLUSION: Ischaemia-reperfusion injury decreases the expression of CD44 within the jejunal mucosa. This may contribute to the failure of the gut barrier after such injury.

Animals↗
PubMed1998

In vitro expression of soluble and cell surface-associated CD44 on endometrial cells from women with and without endometriosis.

BACKGROUND: Endometriosis is one of the most common benign gynaecological diseases, and attachment of retrogradely shed viable endometrial cells is considered to be important in its development. CD44 is a multifunctional adhesion molecule that undergoes alternative splicing, giving rise to different isoforms. METHODS: The expression of cell surface-associated CD44 std, v4, v5, v6 and v10 variants before and after cytokine treatment was investigated in endometrial cultures derived from 10 endometriosis patients and 22 women without the disease using immunocytochemistry. The immunoreactivity of soluble CD44 std, v5 and v6 variants was measured in culture medium using an enzyme immunoassay kit. RESULTS: We report on the presence of soluble CD44 in endometrial culture supernatants. In particular, circulating CD44 standard form levels were significantly higher than levels of splice variants. We also found that both epithelial and stromal cells express surface-associated CD44 molecules in a distinct pattern and that this expression is not modulated by tumour necrosis factor (TNF)-alpha or/and interleukin 1 (IL-1) alpha/beta. Finally, cell surface-associated as well as soluble CD44 expression was similar in the two groups. CONCLUSION: Our results indicate that endometrial cells can serve as a source of circulating CD44, but a direct role in the pathogenesis of endometriosis is rather improbable.

Alternative Splicing↗
PubMed2003

A novel CD44 antibody identifies an epitope that is aberrantly expressed on acute lymphoblastic leukaemia cells.

Previous studies have shown that the antibody 7H9D6 identifies CD44, a glycoprotein receptor for hyaluronic acid. 7H9D6 recognizes an epitope of CD44 that is not always present on CD44 molecules. The 7H9D6 antibody bound to the hyaluronic acid binding domain of CD44 and inhibited cell adhesion to immobilized hyaluronic acid. However, the expression of the 7H9D6 epitope was not sufficient for hyaluronic acid binding. Immunofluorescent staining with 7H9D6 revealed a punctate surface staining pattern, suggesting that CD44 molecules recognized by 7H9D6 are located in clusters on the cell surface. In contrast, other CD44 antibodies produced a uniform staining pattern. Early bone marrow B cells were negative for 7H9D6 but reactive with other CD44 monoclonal antibodies. In contrast, leukaemic cells from 65% of patients (28 of 43) with B lineage acute lymphoblastic leukaemia bound 7H9D6. Patients expressing the 7H9D6 epitope on their leukaemic cells had an increased risk of death (HR 3.5 95% CI 1.1-10.9, P = 0.029) and of disease relapse (HR 3.2 95% CI 1.2-8.5, P = 0.017) when corrected for white cell count. This antibody may be useful for the detection of residual disease in B lineage acute lymphoblastic leukaemia and as a prognostic indicator and for the study of CD44 function.

Adolescent↗
PubMed2000

CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells.

Shigella entry into epithelial cells is characterized by a transient reorganization of the host cell cytoskeleton at the site of bacterial interaction with the cell membrane, which leads to bacterial engulfment in a macropinocytic process. Using affinity chromatography on HeLa cell extracts, we show here that the hyaluronan receptor CD44 associates with IpaB, a Shigella protein that is secreted upon cell contact. Overlay and solid-phase assays indicated that IpaB binds directly to the extracellular domain of CD44; binding is saturable and inhibitable, with a half-maximal inhibitory concentration of 175 nM. Immunoprecipitation experiments showed that IpaB associates with CD44 during Shigella entry. CD44 is recruited at bacterial entry sites and localizes at the plasma membrane of cellular extensions induced by Shigella. Pretreatment of cells with an anti-CD44 monoclonal antibody resulted in inhibition of Shigella-induced cytoskeletal reorganization, as well as inhibition of bacterial entry, whereas transfection of CD44 in cells that are deficient for CD44 results in increased bacterial binding to cells and internalization. The IpaB-CD44 interaction appears to be required for Shigella invasion by initiating the early steps of the entry process.

Antibodies, Monoclonal↗
PubMed1996

Accumulation of p53 and expression of CD44 in human prostatic cancer and benign prostatic hyperplasia: an immunohistochemical study.

OBJECTIVE: To investigate the expression of mutant p53 and wild-type CD44 in human benign and neoplastic prostate. PATIENTS AND METHODS: The accumulation of p53 and the expression of CD44 were investigated immunohistochemically in formalin-fixed and paraffin-embedded tissue specimens (obtained by transurethral resection and open prostatectomy) from 16 patients with primary prostatic cancer (median age 65 years, range 54-75) and six patients with benign prostatic hyperplasia (BPH) (median age 67 years, range 58-75). RESULTS: Positive immunoreactivity for p53 and CD44 was detected in six and eight samples of prostatic cancer tissue, respectively. Additionally, all six prostatic cancer samples showing positive immunoreactivity for p53 were also positive for CD44. There were more samples expressing p53 and CD44 in prostatic cancer with a high Gleason grade score than in samples from cancer with a lower score. In samples from six patients with BPH, positive immunoreactivity for p53 and CD44 was observed in one and two, respectively; stained cells were restricted to the secretory cell layer of the gland. CONCLUSIONS: There was an association between prostatic tumour grade and the increasing expression of p53 and CD44, although there were too few samples for statistical significance. The staining pattern of cells expressing p53 and CD44 may be different between prostatic cancer and BPH tissues.

Aged↗
PubMed1996

Semiquantitative Detection of Abnormal CD44 Transcripts in Colon Carcinomas by Reverse Transcription-Polymerase Chain Reaction Enzyme-linked Immunosorbant Assay (RT-PCR ELISA).

Background: Abnormal expression of CD44 variant RNA has been detected in a variety of human tumors and has been shown to be a potential diagnostic marker. To date, such analysis requires time-consuming gel electrophoresis, blotting, and autoradiographic procedures, and this approach may not be suitable for routine laboratory examinations. We have developed a rapid and semiquantitative reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA) method and used it to analyze CD44 expression in colon carcinoma tissues and exfoliated cancer cells in colon luminal washings. Methods and Results: RNA was extracted from sample cells and tissues and converted to cDNA. PCR amplification products, labeled by incorporation of digoxigenin-11-dUTP, were hybridized with biotinylated probes complementary to CD44 exon 12 or to exons in the standard portion (CD44s) of the gene. Hybridized DNA complexes were immobilized on streptavidin-coated microtiter plates, and the bound PCR products were detected with a peroxidase-conjugated antibody to digoxigenin. CD44-derived PCR products were quantified by absorbance of a chromogenic reaction. Elevated expression of CD44 variant exon 12 was detected initially by Southern blot analysis in all of the 9 colon carcinoma tissues, while weak expression was observed in only 3 of 9 normal mucosas. This tumor-related differential expression was confirmed by the newly developed PCR-ELISA method. Elevated expression of CD44 exon 12 was also detected in exfoliated colonic epithelial cells from 10 of 13 carcinoma cases but not in exfoliated cells from 4 patients with inflammatory bowel disease. Conclusions: Raised expression of CD44 variant exon transcripts can be detected reliably in colonic tumor tissue and in exfoliated colonic cancer cells by a semiquantitative RT-PCR ELISA method. This was shown to be as sensitive as conventional RT-PCR using chemiluminescent detection. Therefore, CD44-based RT-PCR ELISA could facilitate detection of neoplasia in clinical specimens including colon washings and naturally micturated urine.

Journal Article↗
PubMed2002

Expression of CD44 variants in colorectal carcinoma quantified by real-time reverse transcriptase-polymerase chain reaction.

CD44 is a family of transmembrane glycoproteins that has been linked to carcinogenesis and metastasis. It serves as a major receptor for hyaluronate. The v3 isoform binds to growth factors through heparan sulfate side chains and targets these factors to their high-affinity signal transducing receptors. The purpose of this study was to analyze the expression of CD44 v3 and v4 in human colorectal carcinoma with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Our results show that 19 of 56 cases (33.9%) showed a greater than 2-fold increase in CD44 v3 expression in tumors as compared with matched normal mucosa, while 15 of 44 cases (34.1%) showed a greater than 2-fold increase in CD44 v4 expression. There was a marked variation in fold-differences of CD44 gene expression between tumor and normal samples (T/N ratios) among the tumors. This prompted us to correlate the T/N ratios of the tumors with clinicopathologic characteristics. Interestingly, overexpression of CD44 v3 mRNA was associated with the presence of vascular invasion (P <.05). Similarly, overexpression of CD44 v4 was significantly correlated to increased depth of invasion (P <.05). Results from the present study suggest that overexpression of CD44 v3 and v4 mRNA levels may be useful clinical markers for colorectal carcinoma invasiveness.

Adult↗