Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Single tumor cell”

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 19 recordsLinked to original sources
PubMed2025

Mismatch-introduced crRNA guided PCR-CRISPR/Cas12a platform improves EGFR point mutation detection in single tumor cell.

Dynamic monitoring of epidermal growth factor receptor (EGFR) mutations is essential for the early identification of resistance and treatment adaptation. Single-cell heterogeneity analysis is crucial for precision cancer medicine, yet sensitive and specific detection methods for individual tumor cells remain challenging. Here, we develop a PCR-CRISPR/Cas12a platform enhanced by the incorporation of mismatched base in crRNA at specific site for single-cell point mutation detection. This platform demonstrated high specificity and sensitivity, detecting point mutation at a frequency of 0.1% and in as low as 1.02 ng of genomic DNA, which represents an improvement over the amplification-refractory mutation system PCR (ARMS-PCR). Notably, the accuracy of the platform is highly consistent with next-generation sequencing (NGS), as evidenced by Kappa test values surpassing 0.9. By utilizing a conical-pore membrane with optimized porosity for single circulating tumor cell (CTC) enrichment, our platform enables point mutations detection in individual tumor cells, offering potential enhancements in precision and reliability for EGFR mutation analysis. This novel methodology holds potential for more accurate and personalized cancer treatment strategies.

Humans↗
PubMed1991

Demonstration of estrogen and progesterone receptors as well as Ki-67 and p-145 antigens in single tumor cells from blood and pleural effusions using a slide assay.

We describe a slide assay that allows the demonstration of antigens localized in the nucleus from isolated white blood cells as well as from single tumor cells derived from malignant effusions. With the antibodies Ki-67 and anti-p-145 an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas. An almost identical reaction was obtained when tumor cells from malignant effusions were tested. Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of normal mesothelial cells from non-tumorous cavity fluids. The detection of estrogen and progesterone receptors (ER and PR) localized in the cell nucleus can be achieved by the same assay. The reaction is enhanced by incubation of the tumor cells for 30 min at 37 degrees C prior to fixation. Pleural effusions from 20 patients with breast cancer were tested. ER was positive in 13 and PR was positive in 12 of the 20 samples. In 5 cases there was a divergent reaction with ER and PR antibody. The hormone receptors of the primary tumor were known in 15 (ER) and 14 (PR) patients, respectively. In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated tumor cells from the pleural effusions. These results indicate that the demonstration of hormone receptor proteins in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer.

Breast Neoplasms↗
PubMed2006

A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel.

A microfluidic device was developed for quantifying the migratory and deformability capabilities of a single tumor cell using direct imaging. It was fabricated using photolithography and is made of polydimethysiloxane. Chemotaxis approach was used for directing cell movement, using 10 microm microgaps to restrict the migration to a single cell. Each cell's migration rate is quantified as a measure of its distance traveled over time taken. Real-time recording of cell deformation under physiological flow was performed, and the elongation index and surface area change of the cells were compared. Three human tumor cell lines viz. HepG2, HeLa and MDA-MB-435S were used to verify the operation and methodology of the device. Their migration rates ranged from 5 to 15 microm/h, consistent with other scientific reports. By reducing the microgap width to 3 microm, it was found that the cells moved along the row of microgaps but were unable to migrate across the microgaps. Subsequent deformation of the cells through the gaps further showed that their migratory capability might be governed by their deformation ability and the deformation stress on their membranes. The strategy of targeting cancer cell membrane for rupture may provide a therapy for metastasis. Being a valuable tool for rapid quantification of a single cell's migratory capability, this device should be helpful for pharmacologic and drug screening, investigation of factors that regulate cell migration and deformation.

Algorithms↗
PubMed1999

Multiple mutation analyses in single tumor cells with improved whole genome amplification.

Combining whole genome amplification (WGA) methods with novel laser-based microdissection techniques has made it possible to exploit recent progress in molecular knowledge of cancer development and progression. However, WGA of one or a few cells has not yet been optimized and systematically evaluated for samples routinely processed in tumor pathology. We therefore studied the value of established WGA protocols in comparison to an improved PEP (I-PEP) PCR method in defined numbers of flow-sorted and microdissected tumor cells obtained both from frozen as well as formalin-fixed and paraffin-embedded tissue sections. In addition, the feasibility of I-PEP-PCR for mutation analysis was tested using clusters of 50-100 unfixed tumor cells obtained by touch preparation of ten breast carcinomas by conventional sequencing of exon 7 and 8 of the p53 gene. Finally, immunocytochemically stained microdissected single disseminated tumor cells from bone marrow aspirates were investigated with respect to mutations in codon 12 of Ki-ras by restriction fragment length polymorphism (RFLP)-PCR after I-PEP-PCR. The modified I-PEP-PCR protocol was superior to the original PEP-PCR and DOP-PCR protocols concerning amplification of DNA from one cell (efficiency rate I-PEP-PCR 40% versus PEP-PCR 15% and DOP-PCR 30%) and five cells (efficiency rate I-PEP-PCR 100% versus PEP-PCR 33% and DOP-PCR 20%). Preamplification by I-PEP allowed 100% sequence accuracy in > 4000 sequenced base pairs and Ki-ras mutation detection in isolated single disseminated tumor cells. For reliable microsatellite analysis of I-PEP-preamplified DNA, at least 10 unfixed cells from fluorescence-activated cell sorting, 10 cells from frozen tissue, or at least 30 cells from formalin-fixed and paraffin-embedded tissue sections were required. Thus, I-PEP-PCR allowed multiple reliable microsatellite analyses suited for microsatellite instability and losses of heterozygosity and mutation analysis even at the single cell level, rendering this technique a powerful new tool for molecular analyses in diagnostic and experimental tumor pathology.

Bone Marrow Neoplasms↗
PubMed2002

Single tumor cell uptake and dosimetry of technetium-99m Fab' or minute anti-CD22 in low-grade B-cell lymphoma.

BACKGROUND: A patient with follicular lymphoma was investigated with 0.5 mg Fab' or minute anti-CD22 labeled with 1100 MBq technetium-99m ((99m)Tc). A computed tomography scan performed a week later revealed regression. This unexpected response prompted an investigation of single cell dosimetry of low-energy electron emitters. METHODS: Another patient with low-grade, unclassifiable B-cell lymphoma with a low expression of CD22 was injected with (99m)Tc anti-CD22. Blood samples were drawn 30 minutes, 4 hours, and 24 hours after injection. Lymphoma cells (CD19+) and T cells (CD3+), which served as control cells, were separated using a flow cytometer. The radioactivity of the two cell populations was measured in an NaI(Tl) well-type detector. The mean uptake per cell and absorbed dose were calculated. The CD22 expression of the patient's cells and of a B-cell lymphoma cell line (Raji) were assessed by flow cytometry for the extrapolation of the absorbed dose from the patient's cells to a cell line with higher CD22 expression. RESULTS: The average number of (99m)Tc atoms per CD19+ and CD3+ cell 4 hours postinjection were 5.4 and 0.054, respectively. Depending on the assumed ratio between antibody and CD22 molecules (1:2 or 1:1), the CD22 expression on the patient's cells and Raji cells varied from 2800 to 5700 and from 37,000 to 74,000 per cell, respectively. The average absorbed dose per cell ranged from 4 x 10(-7) to 0.1 grays (Gy). CONCLUSIONS: It seems feasible to assess the mean single tumor cell uptake of (99m)Tc targeted by Fab' or minute anti-CD22 in a patient's lymphoma using sorted cell populations, thereby allowing single cell dosimetry. Extrapolation of the absorbed dose from (99m)Tc to cells with higher CD22 expression was made and under certain conditions absorbed doses of 0.1 Gy were obtained, indicating the potential relevance of low-energy electron emitters to therapy.

Antigens, CD↗
PubMed1984

Radioisotope-decay model of carcinogenesis: multistep process in the formation of original single tumor cells induced by 3-methylcholanthrene in mice.

The times of origin of fibrosarcomas induced with 3-methylcholanthrene in mice were analyzed mathematically. Histograms of the rates of formation of original single tumor cells plotted against the time after carcinogen treatment fitted a two-step exponential decay function. This model was named a radioisotope-decay model by analogy with the multistep decay of radioisotopes. The half-lives of the initial and intermediate transient states were determined for three tumor groups, and were found to be 23-29 days for both states. The present study indicates the involvement of at least two steps in the establishment of tumors, even with a complete carcinogen.

Animals↗
PubMed1991

Resistance of single tumor cells and their intracellular compartments to lipid peroxidation.

An attempt was made to analyze heterogeneity of tumor populations with respect to potential stability of single cells and their intracellular compartments (lipid-containing refractory granules, RG, and cytoplasmic sites) to lipid peroxidation (LP). LP was initiated by a combined action of hypoxia and u.v.-light and measured by the level of fluorescent product of lipid peroxidation (FPLP) well distinguished from other fluorescent components of the cell. Irrespective of the cell growth stage, RG were found to make a major contribution to the total intensity of FPLP of the cell. However, this contribution was minimal (20 to 30%) in exponentially growing ascites tumor cells and maximal (70 to 90%) in the stationary growing ones. It is noteworthy that in both cases the heterogeneous tumor population has cells with a high stability to inhibitory and cytokilling action of LP. We believe that the approach suggested in this work is of potential importance for experimental and clinical practice since it is highly sensitive for detecting FPLP in single cells, which allows one to reveal various subcellular tumor populations and estimate their stability to LP.

Animals↗
PubMed2006

Heterogeneity of neoplastic cells in B-cell chronic lymphoproliferative disorders: biclonality versus intraclonal evolution of a single tumor cell clone.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphoproliferative disorders (B-CLPD) are usually monoclonal expansions of a single B-cell clone. However in some cases, two unrelated B-cell clones co-exist. Additionally, cases with two B-cell subpopulations displaying a similar phenotype but distinct DNA contents exist, the exact nature of these cases remaining unknown. In order to gain insight into the characteristics of these complex B-CLPD we examined two cohorts of patients. MATERIAL AND METHODS: One cohort had two phenotypically distinct B-cell populations (group A; n= 9) and the other, two B-cell subsets showing different DNA contents and/or light scatter properties, but a similar immunophenotype (group B; n= 7). RESULTS: Fluorescent in situ hybridization studies revealed the presence of genetic abnormalities in six cases from group A, either in one (n=5) or the two co-existing B-cell populations (n=1); in all these cases the two B-cell populations showed unrelated IgH gene rearrangements. In all seven cases from group B, the B-cell population showing higher DNA contents had additional chromosomal abnormalities as compared to the other subset; molecular analysis confirmed the monoclonal nature of these cases. INTERPRETATION AND CONCLUSIONS: In summary, we show that in group A, two phenotypically/cytogenetically distinct, unrelated B-cell clones co-exist, while the two B-cell populations from group B appear to represent different stages of evolution of a single clone.

Base Sequence↗
PubMed1986

Evidence that intravenously derived murine pulmonary melanoma metastases can originate from the expansion of a single tumor cell.

The purpose of these studies was to determine whether hematogenous clonal pulmonary melanoma metastases originate from the expansion of a single cell and if so, by extrapolation, metastasis can be considered a cloning process. Three different cell lines of murine K-1735 melanoma with different metastatic properties and unique karyotypes were injected i.v. into syngeneic C3H/HeN mice as multicell aggregates of individual cell lines or combinations of cell lines. Resultant solitary lung metastases were isolated in culture as individual lines and then karyotyped. Even when heterogeneous clumps of tumor cells were injected, the individual metastases exhibited a karyotype unique to one metastatic cell type. Furthermore, when cellular aggregates were composed of metastatic cells admixed with cells that were tumorigenic but nonmetastatic, the resultant metastases exhibited only the karyotype of the metastatic cells. This finding suggests that the presence of metastatic cells did not change the inability of nonmetastatic cells to proliferate in a distant organ. Collectively, the results indicate that the resultant metastases were of clonal origin owing to the expansion of a single metastatic tumor cell in the lung parenchyma.

Animals↗
PubMed2002

Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer.

OBJECTIVE: To evaluate the clinical relevance of real-time quantitative polymerase chain reaction (qPCR) detection of CEA and CK20 transcripts, as potentially related to tumor cell dissemination, in blood and peritoneal lavage from patients undergoing surgery for colorectal cancer. SUMMARY BACKGROUND DATA: Dissemination of single colorectal cancer cells in the peritoneal cavity, as well as in tumor drainage and peripheral blood vessels, might play a role in the metastasis process, thus affecting the clinical course. However, this phenomenon needs further elucidation. METHODS: In a prospective study the authors evaluated the potential of qPCR in the detection of CEA and/or CK20 transcripts in the peritoneal lavage fluid and in the peripheral and mesenteric venous blood of 39 patients undergoing curative resection for colorectal cancer. Peritoneal lavage and peripheral blood was sampled before and after tumor resection; mesenteric venous blood was sampled from the major tumor-draining vein immediately before clamping. After RNA extraction and reverse transcription, qPCR was performed using specific cDNA primers and probes for CEA and CK20. The dichotomous results from the qPCR were used as a predictor along with other covariates in Cox proportional hazard regression models of long-term outcome (disease-free survival and overall survival). RESULTS: Of 39 patients, 11 were positive. The median follow-up at analysis was 31 months for all patients. The dichotomous qPCR covariate was significant, with P =.001 and.0035 for disease-free survival and overall survival, respectively, in the proportional hazard regression models with only qPCR. In seven patients, disseminated colorectal cancer cells were found in the peritoneal lavage fluid but not in blood specimens; five of these patients (71%) had recurrence. CONCLUSIONS: These data suggest that detection of mRNA coding for CEA and/or CK20 using qPCR has potential clinical utility as a prognostic marker and should be evaluated in larger clinical studies. Identification of patients at high risk for metastatic disease after curative resection of colorectal cancer might be improved by analyzing peritoneal lavage specimens in addition to blood samples. This is based on the observation that in more than half of qPCR-positive patients, disseminated colorectal cancer cells were detected in peritoneal lavage specimens but not in blood samples, and that 71% of them had recurrence.

Adult↗
PubMed1978

[Rhabdomyosarcoma of the skin--behavior of single tumor cells in vitro].

In vitro growth of individual tumor cells is described, deriving from a rhabdomyosarcoma. There can be suggested two different cell-types: fibroblast-like cells with no particular aspects of morphology, and epitheloid-like cells, recognized from structure and nuclear-behaviour as tumor-giant cells. This methods advantages are discussed as a supplement of histological criteria, as well as its clinical pattern in future.

Aged↗
PubMed1977

Cyclic adenosine 3':5'-monophosphate-mediated insulin secretion and ribosomal protein phosphorylation in a hamster islet cell tumor.

In order to understand the mechanism by which cyclic 3':5'-adenosine monophosphate (cAMP) regulates insulin secretion, cAMP-dependent protein phosphorylation was studied in a transplantable hamster islet cell tumor. Single cell suspensions prepared by enzymatic digestion of the tumors released insulin into the incubation media. Glucagon (3 nM to 3 muM) stimulated cellular cAMP accumulation and insulin release in a dose-dependent manner and these effects were enhanced by 1 mM theophylline. 8-Bromoadenosine 3':5'-monophosphate (8Br-cAMP) (1 mM) increased insulin release. Somatostatin (10 mug/ml) inhibited basal and glucagon or 8Br-cAMP-stimulated insulin release without significantly lowering cellular cAMP in glucagon-stimulated cells. For analysis of phosphoproteins, cells were incubated with carrier-free 32Pi following which lysates were prepared and analyzed by sodium dodecyl sulfate slab gel electrophoresis and autoradiography. Of the numerous 32P-labeled protein bands found, only one (P1, Mr = 28,000) displayed a significant increase in 32P incorporation when cells were incubated under conditions that raise the concentration of cellular cAMP. Somatostatin did not affect 32P incorporation into P1 or any other protein band. When cells were incubated with glucagon, an increase in cellular cAMP was evident after 1 min, enhanced 32P incorporation into P1 after 1 to 5 min, and stimulation of insulin release after 5 to 10 min. Analysis of subcellular fractions led to the designation of P1 as a 40 S ribosomal protein. Two-dimensional electrophoresis of 32P-labeled basic ribosomal proteins showed two labeled proteins, P1 and P2, both of which were localized to the 40 S ribosomal subunit. Only phosphorylation of P1 was stimulated by cAMP. The cAMP-dependent ribosomal phosphoprotein, P1, may be identical with a ribosomal phosphoprotein demonstrated in a variety of tissues and species. Its physiological role remains to be established.

Adenoma, Islet Cell↗
PubMed1996

Single-cell mutation analysis of tumors from stained histologic slides.

Formalin-fixed and paraffin-embedded tissues are a valuable resource for diagnosis and research. PCR is one of the most powerful methods of retrospective analysis of the DNA present in fixed tissues. One major problem with the molecular analysis of tissue samples, however, is cellular heterogeneity, ie, the large variety of cell types usually present in these specimens can mask cell-specific genetic alterations associated with disease. Herein we describe a procedure for obtaining and analyzing single cells recovered from stained histologic tissue sections without risking contamination from neighboring cells. An ultraviolet laser microbeam was used to physically destroy the tissue surrounding the single cells of interest. These cells, now freed from adjacent cells, were then easily retrieved with a motorized, computer-controlled micromanipulator and molecularly characterized through the use of PCR-based microanalysis. This accurate microdissection technique, followed by DNA amplification and direct sequencing, revealed a novel mutation in the gene coding for the cell adhesion molecule E-cadherin in single tumor cells that was absent in the adjacent single epithelial cells of a patient with early gastric cancer of the diffuse type. In this form of malignancy, tumor cells lose homophilic cell-to-cell interactions and invade the connective tissue as single cells. E-cadherin gene mutations have previously been detected in advanced diffuse-type gastric cancer and gastric carcinoma cell lines. The present study suggests that E-cadherin gene mutations may be an early event in gastric tumorigenesis. The laser-based isolation and subsequent molecular characterization of individual cells, as described herein, allows for micrometer-sized precision and should prove useful in detecting the nucleic acid abnormalities that underlie cancer, infection, and genetic disease.

Base Sequence↗
PubMed1988

Renal-cell carcinoma with intranuclear inclusions metastatic to thyroid: a diagnostic problem in aspiration cytology.

A case of renal-cell carcinoma (RCC) exhibiting prominent intranuclear inclusions in a metastasis to the thyroid is presented. RCC had been treated in this patient by right nephrectomy 7 yr earlier and by left partial nephrectomy 5 yr earlier; the patient had also received radiation to the neck 4 yr earlier for carcinoma in situ of the left true vocal cord. Aspiration performed on a rapidly enlarging mass in the left lobe of the thyroid revealed both clusters of tumor cells and single tumor cells with prominent intranuclear inclusions. Definitive distinction between a primary and metastatic neoplasm was difficult on the aspiration specimen. Subsequent thyroidectomy confirmed the diagnosis of metastatic renal-cell carcinoma with intranuclear inclusions by histologic, immunohistochemical, and ultrastructural analysis. The differential diagnosis by aspiration cytology of thyroid neoplasms that contain intranuclear inclusions is discussed.

Aged↗
PubMed2003

Comparison of pathologist-detected and automated computer-assisted image analysis detected sentinel lymph node micrometastases in breast cancer.

Sentinel lymph node biopsy has stimulated interest in identification of micrometastatic disease in lymph nodes, but identifying small clusters of tumor cells or single tumor cells in lymph nodes can be tedious and inaccurate. The optimal method of detecting micrometastases in sentinel nodes has not been established. Detection is dependent on node sectioning strategy and the ability to locate and confirm tumor cells on histologic sections. Immunohistochemical techniques have greatly enhanced detection in histologic sections; however, comparison of detection methodology has not been undertaken. Automated computer-assisted detection of candidate tumor cells may have the potential to significantly assist the pathologist. This study compares computer-assisted micrometastasis detection with routine detection by a pathologist. Cytokeratin-stained sentinel lymph node sections from 100 patients at the University of Vermont were evaluated by automated computer-assisted cell detection. Based on original routine light microscopy screening, 20 cases that were positive and 80 cases that were negative for micrometastases were selected. One-level (43 cases) or two-level (54 cases) cytokeratin-stained sections were examined per lymph node block. All 100 patients had previously been classified as node negative by using routine hematoxylin and eosin stained sections. Technical staining problems precluded computer-assisted cell detection scanning in three cases. Computer-assisted cell detection detected 19 of 20 (95.0%; 95% confidence interval, 75-100%) cases positive by routine light microscopy. Micrometastases missed by computer-assisted cell detection were caused by cells outside the instrument's scanning region. Computer-assisted cell detection detected additional micrometastases, undetected by light microscopy, in 8 of 77 (10.4%; 95% confidence interval, 5-20%) cases. The computer-assisted cell detection-positive, light microscopy-missed detection rate was similar for cases with one (3 of 30; 10.0%) or two (5 of 47; 10.6%) cytokeratin sections. Metastases detected by routine light microscopy tended to be larger (0.01-0.50 mm) than did metastases detected only by computer-assisted cell detection (0.01-0.03 mm). In a selected series of patients, automated computer-assisted cell detection identified more micrometastases than were identified by routine light microscopy screening of cytokeratin-stained sections. Computer-assisted detection of events that are limited in number or size may be more reliable than detection by a pathologist using routine light microscopy. Factors such as human fatigue, incomplete section screening, and variable staining contribute to missing metastases by routine light microscopy screening. Metastases identified exclusively by computer-assisted cell detection tend to be extremely small, and the clinical significance of their identification is currently unknown.

Breast Neoplasms↗
PubMed1993

Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma.

BACKGROUND: Accurate assessment of the presence and absence of tumor in the regional lymph nodes is critical in assessment of prognosis for patients with lung cancer. Development of sensitive immunohistochemical techniques and specific monoclonal antibodies has increased our capacity, in melanoma and breast cancer, to detect small groups of tumor cells or even single tumor cells in lymph nodes that appear to be tumor free in conventionally stained sections. PURPOSE: This retrospective study was designed to assess whether use of a polyclonal antikeratin reagent in immunohistochemical analysis offers any advantage over conventional histopathology in detection of regional lymph node metastases in non-small-cell lung cancer. METHODS: Paraffin-embedded tissue sections from regional lymph nodes of 65 patients with non-small-cell lung cancer were studied. We examined tissue from 588 nodes of 60 patients with a diagnosis of disease confined to the lung and from 72 nodes of five patients with a diagnosis of metastasis to some nodes. A polyclonal antikeratin antibody was applied to the lymph node tissue sections, using the avidin-biotin complex immunoperoxidase technique. RESULTS: Single tumor cells and small clusters of tumor cells (occult micrometastases) not visible on routine evaluation were readily detected in 38 (63%) of the 60 patients whose nodes appeared to be negative on examination of hematoxylin-eosin-stained slides. In the five patients with a diagnosis of node-positive non-small-cell lung cancer, five (10%) of 51 nodes that were tumor free on conventional examination contained metastases. Metastatic tumor cells were most often located in the subcapsular or medullary sinuses. The lymph nodes that contained occult tumor cells were those located nearest to the tumor, mainly in peribronchial and hilar locations. The median survival of patients with occult metastases (1977 days) was shorter than that of patients whose nodes contained no tumor (2456 days) but was longer than that of patients whose nodes contained metastases detectable on hematoxylin-eosin-stained slides (927 days). CONCLUSIONS: Our results suggest that, in patients with non-small-cell lung cancer, metastatic involvement of regional lymph nodes is more frequent than was previously determined by the conventional histologic method and substantially more frequent than in other tumor types, such as melanoma and breast cancer. IMPLICATIONS: The high frequency of occult nodal metastases in non-small-cell lung cancer makes it clear that, without immunohistochemistry, disease is understaged in many patients. Therefore, it seems essential that immunohistochemical evaluation of the lymph nodes be undertaken in clinical trials.

Adult↗
PubMedDate not supplied

Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors.

In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strongly expressed by single tumors cells invading adjacent brain tissue at the infiltrative margin. Neither the expression pattern in primary and secondary glioblastomas nor in the precursor tumors revealed significant differences. There was also no intraindividual constant expression pattern during glioma progression or correlation with malignancy. Restricted expression of CD44s, galectin-3, tenascin and N-CAM in solid tumor masses seems to contribute to homotypic tumor cell adhesion while single tumor cells abolish this expression profile and acquire invasive activities by expression of cathepsin D, MMP-2 and MMP-9.

Adult↗