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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In different human tumors, splice variants of the surface glycoprotein CD44 (CD44v) are correlated with advanced stages of tumor growth and metastatic potential. In breast cancer and colon cancer, expression of epitopes encoded by exon v6 on primary tumors is an independent prognostic factor for poor patient survival. Two different screening methods for the detection of CD44 variants in tumors have been applied: immunohistochemistry (IHC) and semi-quantitative reverse transcription PCR (RT-PCR). In this study, we have compared the predictive capacity and the applicability of both approaches, using 31 human breast-tissue specimens (normal and neoplastic). IHC reveals lack of expression of CD44v on normal ductal epithelial cells but strong expression on myoepithelial cells. The majority of tumors express CD44 epitopes encoded by several variant exons. RT-PCR detects splice variants in normal epithelium, probably derived from RNA expressed in the myoepithelium. In tumors, RT-PCR reveals expression of a wide range of splice variants, including new ones that are not detected in normal breast tissue, e.g. ones that contain all variant exons. The conclusion of this comparison is that IHC is the better method for breast-tumor sample screening but that the increased sensitivity of RT-PCR can help to distinguish CD44v-positive from CD44v-negative tumors in cases where only a few tumor cells express variants or where epitopes are masked.
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PMID:Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer. 753 Feb 37

CD44 is a cell surface receptor that has been implicated in lymphocyte homing, hematopoiesis, cell migration and possibly also tumor metastasis. In the present study, expression of CD44 variant (CD44v) isoforms was analyzed in 23 lung cancer specimens together with corresponding normal lung tissues by Southern blot analysis coupled with reverse transcription-polymerase chain reaction amplification. We found that CD44v isoforms were expressed in all lung cancer specimens, suggesting a possible role in the establishment of metastases by these highly malignant tumors, but normal tissues were also positive. This is in marked contrast to the previous reports of essentially negligible expression of CD44v isoforms in normal colon and breast, and suggests a physiological function in the lung.
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PMID:Expression of CD44 variant isoforms in normal and neoplastic cells of the lung. 753 Feb 40

The family of related cell surface adhesion molecules designated CD44 are multifunctional proteins displayed by a wide variety of normal and malignant tissues. CD44 properties in vitro include hyaluronate-mediated adhesion, motility, hyaluronate degradation, self-aggregation, and adhesion to lymphoid tissue. These properties are among several that are required by invasive and metastatic tumor cells. Several in vivo experiments indicate that tumor cells transfected to overexpress specific CD44 isoforms display an enhancement in metastatic potential. Numerous CD44 isoforms exist as a result of alternative splicing, and specific isoforms enhance tumor cell metastasis more efficiently than others. This suggests that regulation of CD44 alternative splicing is an important determinant of metastatic potential. Several human tumors display specific alterations in CD44 isoform expression, and the extent of clinical disease in specific tumors correlates with the CD44 isoform expression pattern. In this review we analyze these data that suggest that CD44 plays an important role in tumor metastasis.
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PMID:The CD44 adhesion molecule and metastasis. 753 1

We have identified a novel ligand for CD44, a cell surface glycoprotein implicated in tumor metastasis and lymphocyte homing. When the mouse T cell line CTLL-2 was transfected with cDNA encoding a hemopoietic form of mouse CD44, CTLL-2 cells exhibited a new self-adhesive phenotype, forming large aggregates. The aggregation was blocked by neutralizing anti CD44 monoclonal antibody but unaffected by hyaluronidase, indicating the involvement of CD44 and its non-hyaluronate ligand in the cell aggregation. The ability to induce CD44-dependent aggregation was found in culture supernatants of CTLL-2 and its CD44 transfectants. The use of CD44-immunoglobulin chimeric protein revealed that CTLL-2 and its transfectants synthesized a large-molecular weight protein (gp600) which bound specifically to CD44. The gp600 was readily labeled with radioactive sulfate, and treatment of gp600 with chondroitinase ABC or ACII generated a lower molecular weight species (18-22 kDa), suggesting that gp600 consists of a small core protein with chondroitin sulfate glycosaminoglycan side chains. However, binding of CD44 to glycosaminoglycans such as chondroitin 4-sulfate, chondroitin 6-sulfate, and dermatan sulfate was undetectable, suggesting either that a novel chondroitin-type glycosaminoglycan is recognized by CD44 or that a particular configuration of the glycosaminoglycan is required for recognition by CD44.
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PMID:A sulfated proteoglycan as a novel ligand for CD44. 2292 40

Cell adhesion molecules are of pivotal importance during organogenesis and fulfil important functions in maintaining normal organ architecture in the adult. Furthermore, they are involved in diverse and specialized functions such as migration and activation of leukocytes in immunosurveillance and inflammation, and homophilic as well as heterophilic interactions of cells with others and the extracellular matrix. In tumors, various cell adhesion molecules play a role in the complex process of tumor dissemination including metastatic spread. In addition, immunohistochemical detection of certain cell adhesion molecules in tumors has been shown to be of value in predicting the clinical course of the tumor disease. This short review focuses on the polysialic acid of the neural cell adhesion molecule NCAM, integrins and CD44.
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PMID:[Tumors--disorders of cell adhesion]. 753 90

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
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PMID:Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice. 753 41

Changes in glycoconjugate production have been reported for tumor cells. In this study, we investigated the glycoconjugate expression pattern in normal human melanocytes and in a panel of 6 human melanoma cell lines with different metastatic capacity after s.c. inoculation into nude mice. Glycoconjugates were labeled in vitro with [35S] sulphate and [3H] glucosamine, purified from cells and culture medium by column chromatography and identified by treatment with specific glycosidases. Characterization of the purified glycoconjugate fractions as well as alcian-blue staining of xenograft lesions revealed that hyaluronic acid (HA) is the main glycoconjugate produced by all cell lines. Highly metastatic cell lines expressed higher levels of HA than melanocytes and than weakly metastatic or non-metastatic cell lines. In addition, a shift in dominance from chondroitin-sulphate proteoglycan to heparan-sulphate proteoglycan was observed with increasing metastatic capacity. We also studied the expression and binding activity of the HA receptor CD44. Immunoprecipitation experiments indicated high CD44 synthesis only in highly metastatic cell lines, but FACS analysis demonstrated approximately the same surface expression in melanocytes as in all cell lines. Adhesion assays to immobilized HA showed that CD44 can be present in an inactive or an active conformation. Our data suggest that a combination of increased HA production and the expression of CD44 on the cell surface may be associated with high metastatic potential of human melanoma cell lines in nude mice.
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PMID:Glycoconjugate profile and CD44 expression in human melanoma cell lines with different metastatic capacity. 753 56

The lymphocyte adhesion molecule CD44 recognizes a non-hyaluronate proteoglycan, gp600, secreted by mouse T cell line CTLL2. We now demonstrate that gp600 is identical to serglycin, a member of the small proteoglycan family stored in intracellular secretory granules of lymphoid, myeloid, and some tumor cells. Purified gp600 has the ability to bind specifically to CD44, and the binding is dependent on activation of CD44. The CD44-binding elements on gp600 or serglycin are glycosaminoglycans consisting of chondroitin 4-sulfate. Serglycin is readily exocytosed, and its interaction with active form CD44 augments the CD3-dependent degranulation of CD44 positive CTL clones. We conclude that the serglycin secreted from secretory granules of hematopoietic cells is a novel ligand for CD44, and could regulate lymphoid cell adherence and activation.
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PMID:A novel ligand for CD44 is serglycin, a hematopoietic cell lineage-specific proteoglycan. Possible involvement in lymphoid cell adherence and activation. 753 71

We investigated glioblastoma multiforme (GBM) for a pattern of consistent alterations in cell adhesion molecules (CAM) expression that might distinguish tumor from normal autologous brain tissue. We used frozen section immunohistochemistry with anti-CAM and computerized image analysis to quantify staining intensity which we expressed as relative intensity units (RIU). Our results showed that normal brain tissue generally did not express alpha 1 beta 1, intercellular CAM-1 (ICAM-1), and sialylated Lewisx, slightly expressed alpha 2, alpha 4, alpha 5, alpha 6 beta 1, alpha v beta 3, lymphocyte function-associated antigen-3 (LFA-3), Lewisx, sialylated LewisLewisx, had a good expression of alpha 3 beta 1 and CD44, and strongly expressed neural CAM (NCAM). GBM expressed alpha 2, alpha 3, alpha 5, alpha 6 beta 1, alpha v beta 3, ICAM-1, LFA-3, CD44, Lewisx, sialylated Lewisx, and sialylated LewisLewisx significantly higher (2-11-fold RIU) than normal brain tissue. ICAM-1 and LFA-3 were the most distinctive markers of GBM. The small blood vessel endothelial cells of the normal brain and the GBM showed a few differences. The tumor endothelium expression of alpha 2 beta 1, alpha 4 beta 1, and LFA-3 RIU appeared twice higher than in normal endothelium and alpha 6 beta 1 showed an average of 40% RIU decrease in comparison to normal. These results show that the expression of several CAM is consistently altered in GBM and its microvasculature when compared with autologous normal brain tissue.
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PMID:Comparison of cell adhesion molecule expression between glioblastoma multiforme and autologous normal brain tissue. 753 88

The cell-surface receptor for hyaluronic acid, CD44, is expressed by both normal and malignant cells. Numerous CD44 isoforms have recently been identified that are derived by alternative ribonucleic acid splicing. The expression of some CD44 isoforms has been shown to be involved in tumor progression and metastatic spread in a rat carcinoma model and in human carcinomas. In the present study, CD44 isoform expression was evaluated by reverse transcriptase-polymerase chain reaction (PCR) analysis in frozen sections derived from three samples of normal brain tissue and from 40 brain tumors, including samples of glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, cerebral primitive neuroectodermal tumor, medulloblastoma, metastatic colon carcinoma, and metastatic melanoma. Normal brain tissue adjacent to the tumors was also examined in 14 of 18 glioblastomas. In all normal brain and tumor samples, with the exception of metastases from colon carcinoma, PCR analysis demonstrated one prominent product that corresponded to the CD44H hematopoietic form of CD44. Metastases from colon carcinoma demonstrated two prominent PCR amplification products corresponding to CD44H and CD44R1. These results suggest that CD44H is the predominant isoform of this protein in normal human brain tissue and in human neuroectodermal tumors of varying degrees of malignancy. The ability of CD44H to mediate tumor cell motility and invasiveness (in contrast to CD44R1) suggests that the CD44 alternative splicing pattern of neuroectoderm-derived tumors may enhance their local biological aggressiveness and intracerebral spread. The lack of expression of larger molecular weight CD44 variants by primary brain tumors may also partially explain why these tumors rarely metastasize to distant sites.
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PMID:Alternative RNA splicing of the hyaluronic acid receptor CD44 in the normal human brain and in brain tumors. 753 36


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