Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our knowledge of prostate cancer is less well-defined than our knowledge of cancers of other organs. In the colon, for example, morphological criteria to identify carcinomas in situ and some putative preneoplastic lesions are clear; phenotypic differences in the expression of enzymes and antigens are documented in experimental models and are starting to be defined in humans. Experimental models of cancer of the liver and colon show evidence that "enzyme-altered foci" are preneoplastic. In these organs, the "normal" context is much clearer than in the prostate. In contrast, in the prostates of men in the same age range as those who develop prostate cancer, morphological aberrations are almost always present, diverse, and poorly understood. Murphy and Gaeta said that, "in the study of prostatic disease..., almost every aspect remains controversial...[and].... many of the 'known facts' concerning prostatic disease are poorly documented..." While being aware that the definitions of all benign and malignant lesions of the prostate are based on complex morphological criteria which must form the contemporary context for comparisons, our laboratory is searching for markers that will permit the identification of putative preneoplastic lesions in the prostate. In our opinion, these changes will not be found most efficiently, if they are present at all, in long established cell lines, advanced carcinomas, or serially transplantable xenografts of primary prostatic carcinomas. Our preliminary data suggest that several enzyme histochemical and immunohistochemical approaches are worthy of study. Markers that show promise include acid phosphatase, 5'-nucleotidase, leucine aminopeptidase, and CD44.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Putative preneoplastic foci in the human prostate. 752 54

CD44 is a glycosylated adhesion molecule which may undergo alternative splicing of 10 possible exons to generate variant isoforms. A number of CD44 variant isoforms expressed by tumor cells have been correlated with metastatic and proliferative behavior. In this study, we have characterized CD44 isoform expression on three prostate cancer cell lines: ALVA-31, PPC-1, and LNCaP. Using reverse transcriptase-polymerase chain reaction, we have found that ALVA-31 and PPC-1 cells express multiple CD44 isoforms, including CD44s (standard form), CD44E (epithelial form), and an exon 14-containing form. In addition, two smaller forms have been detected: one using an alternative donor splice site within exon 5, and a novel form omitting exon 5 entirely. The CD44 isoforms expressed by ALVA-31 and PPC-1 cells appear to be preferentially located on the cell surface. By contrast, LNCaP cells do not express any of the CD44 forms at the RNA or protein level. Both PPC-1 and ALVA-31 cells display tumorigenesis and invasiveness in nude mice, whereas LNCap cells exhibit a less malignant phenotype, suggesting a correlation between CD44 variant (CD44v) expression and aggressive prostate tumor behavior. Functional characterization reveals that CD44 mediates prostate cell adhesion to extracellular hyaluronic acid (HA). In addition, the CD44 cytoplasmic domain binds specifically to ankyrin, a membrane cytoskeletal protein. Double immunofluorescence labeling and confocal microscopic analyses indicate that HA binding induces the HA receptor (i.e., CD44) to form capped structures. Importantly, intracellular ankyrin is preferentially accumulated underneath HA receptor-capped structures. These results suggest that cytoskeletal proteins such as ankyrin are closely associated with CD44-mediated signaling events induced by HA. Finally, HA-mediated transmembrane interactions between CD44 isoforms and cytoskeletal proteins (i.e. ankyrin) may play a pivotal role in regulating tumor cell behavior during human prostate cancer development.
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PMID:Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells. 754 57

We have examined the expression of the transmembrane glycoproteins CD44 in four human prostate tumor cell lines. Expression was examined at the protein level by flow cytometric analysis and Western blot, and at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR). All four cell lines (DU145, LNCaP, PC3, and ND1) expressed the standard CD44 isoform (CD44s) at the mRNA level and all cell lines except LNCaP expressed CD44s at the protein level. All four cell lines contained one or more isoforms containing the v6 region (exon 10) at the mRNA level, which has been associated with metastatic potential. However, a subpopulation of LNCaP and ND1 cells showed protein expression of v6. In addition, soluble CD44 isoforms were identified in cultured supernatants from all cell lines except LNCaP. These results show that CD44 isoforms are expressed on human prostate tumor cell lines, including the expression of variant isoforms containing the v6 region, and provide a rationale for the further study of this cellular adhesion molecule in prostate cancer. In addition, preliminary results indicate altered expression of CD44 in human prostatic adenocarcinomas examined immunohistochemically.
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PMID:Expression of CD44 isoforms in human prostate tumor cell lines. 889 7

Recent studies suggest that expression of CD44 splice variants are of prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exists between the concentration of soluble CD44 molecules in serum (CD44 standard form and CD44 splice variants v5 and v6) and the prostate cancer stage. Serum levels of these soluble CD44 isoforms were measured by ELISA tests specific for these proteins in controls (n = 30), patients with benign prostatic hyperplasia (BPH; n = 30), with prostate cancer without metastasis (T1,2,3pN0M0; n = 30) and with locally advanced prostate cancer and/or metastatic disease (T3,4pN1,2M1; n = 19). sCD44std and sCD44v6 concentrations were not significantly different among the four groups studied, with few patients' levels outside the central 95% reference intervals. The mean sCD44v5 concentrations of both prostate cancer and BPH patients were significantly lower than those of the controls. There was no significant difference between the soluble CD44 concentrations of the two groups of prostate cancer patients studied. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for providing additional prognostic information on patients with prostate cancer.
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PMID:Soluble CD44 molecules in serum of patients with prostate cancer and benign prostatic hyperplasia. 869 65

CD44s (standard form of CD44) is a transmembrane glycoprotein whose external domain displays extracellular matrix adhesion properties by binding both hyaluronic acid (HA) and collagen. The cytoplasmic domain of CD44s interacts with the cytoskeleton by binding directly to ankyrin. It has been shown that post-translational modifications, such as phosphorylation (by protein kinase C), acylation (by acyl-transferase) and GTP-binding enhanced CD44's interaction with cytoskeletal proteins. Most importantly, the interaction between CD44s and the cytoskeletal protein, ankyrin, is required for the modulation of CD44s cell surface expression and its adhesion function. Recently, a number of tumor cells and tissues have been shown to express CD44 variant (CD44v) isoforms. Using RT-PCR and DNA sequence analyses, we have found that unique CD44 splice variant isoforms are expressed in both prostate and breast cancer cell lines and carcinomas. Most importantly intracellular ankyrin is preferentially accumulated underneath the patched/capped structures of CD44 variant isoform in both breast and prostate cancer cells attached to HA-coated plates. We propose that selective expression of CD44v isoforms unique for certain metastatic carcinomas and their interaction with the cytoskeleton may play a pivotal role in regulating tumor cell behavior during tumor development and metastasis.
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PMID:Involvement of CD44 and its variant isoforms in membrane-cytoskeleton interaction, cell adhesion and tumor metastasis. 875 Jan 86

We have identified that human prostatic cancer cell lines DU145, PC3, ND1, ALVA31 and JCA1 released soluble CD44 molecules and DU145, PC3 and ND1 released soluble CD54. Both soluble and surface CD44 were not found in LNCaP, and both forms of CD54 were not expressed in LNCaP and JCA1. CD54 was found to be highly expressed on cell surface in ALVA31, but these cells did not release soluble CD54. Expression of both cell surface and soluble forms were examined after treatment of cells with IFN-gamma, TGF-beta 1, or culturing in serum-free media. The concentration of soluble CD54 in supernatants changed to small extent after treatment with TGF-beta 1 and increased after treatment with IFN-gamma or in serum-free media. Cell surface expression of CD54 however, changed only minimally after treatment. The levels of cell surface and soluble CD44 also changed minimally after treatment with IFN-gamma and TGF-beta 1 but decreased in serum-free media and this was accompanied by marked elevation of soluble CD44 in supernatants. These data indicate that soluble CD44 might be released from cell surface by shedding whereas alternative splicing is the most likely mechanism of soluble CD54 release.
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PMID:Soluble forms of CD44 and CD54 (ICAM-1) cellular adhesion molecules are released by human prostatic cancer cell lines. 891 63

There is a great need for markers that distinguish slowly progressive from rapidly progressive prostate cancers in paraffin-embedded tissues. CD44, an adhesion molecule that has been useful for the prediction of prognosis in some other cancers, has not been described in prostate cancer. The expression of CD44 was investigated with the monoclonal antibody GKW.A3 in prostate cancer in formalin-fixed, paraffin-embedded tissue sections of (1) whole prostates from 50 patients with 74 prostate cancers; and (2) lymph node metastases from 14 patients. Sixty percent of primary prostate cancers expressed CD44 moderately to strongly. No metastases expressed CD44 moderately to strongly; only 14% of metastases expressed even low levels of immunohistochemically detectable CD44. There is a difference between primary and metastatic prostate cancer (P <.0006) in the expression of CD44 and an inverse correlation (P <.05) between histological differentiation (Gleason grade) and the expression of CD44. The magnitude of the differential expression of CD44 in primary and metastatic prostate cancers suggests it should be investigated as an indicator of prognosis in a large prospective study.
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PMID:Altered expression of CD44 in human prostate cancer during progression. 892 76

Cell adhesion molecules (CAMs) are important in cell-cell interaction and interactions between cells and components of the extracellular matrix. CAMs have been associated with invasion and metastasis in a wide variety of human malignancies, including tumors of the genitourinary tract. Cadherins are transmembrane glycoproteins that bind cells by homophilic, homotypic interactions. Loss of expression of E-cadherin has been associated with dedifferentiation, invasion, and metastasis in prostate cancer and transitional cell neoplasia of the urinary bladder. CD44, a family of transmembrane glycoproteins principally involved in cell-extracellular matrix interactions, also has been associated with invasion and metastasis in urologic malignancies. Through alternative splicing, a variety of CD44 isoforms can be expressed that can undergo extensive posttranslational modification. CD44 variants have been associated with metastasis in a variety of human malignancies, particularly in the gastrointestinal system. Although loss of expression of CD44 standard form has been associated with aggressive prostate gland and bladder cancers, no specific isoform has been associated with metastasis of these neoplasms. Integrins are transmembrane glycoproteins with wide cellular distribution that bind a variety of extracellular matrix components. Integrins have been studied extensively in prostate cancer in which altered integrin expression has been associated with malignant prostatic epithelium. Additional adhesion molecules that have been studied to a variable degree in urologic malignancies include selectins and the immunoglobulin super-family. CAMs are fundamental to diverse biologic processes and appear capable of regulating intracellular signaling events that appear to have significant importance in human malignancy, including cancers of the urogenital tract.
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PMID:Cellular adhesion molecules in urologic malignancies. 898 Mar 68

We have used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rodent prostatic cancer cells to map the location of a metastasis suppressor gene(s). Using this approach, several chromosomal regions have been identified that harbor such metastatic suppressor genes, including human chromosome 11 between p11.2-13 (T. Ichikawa et al., Cancer Res., 52: 3486-3490, 1992, 54: 2299-2302, 1994; N. Nihei et al., Genes Chromosomes & Cancer, 14: 112-119, 1995; C. W. Rinker-Schaeffer et al., Cancer Res., 54: 6249-6256, 1994). Using positional cloning, a metastatic suppressor gene, termed KAI1, was identified, which is located at human chromosome 11p11.2 (5). Overexpression of KAI1 results in metastasis suppression in certain highly metastatic Dunning R-3327 rat prostatic cancer sublines, such as AT6.1, without metastasis suppression in other highly metastatic sublines, such as AT3.1. This suggests that an additional metastasis suppressor gene is located within the human chromosome 11p11.2-13 region. The CD44 gene is located on human chromosome 11p13 and encodes an integral membrane glycoprotein that participates in specific cell-cell and cell-extracellular matrix interactions. Down-regulation of CD44 expression both at the mRNA and protein levels correlates with metastatic potential within the Dunning system of rat prostatic cancer sublines. Transfection-induced enhanced expression of the Mr 85,000 standard form of CD44 in the highly metastatic AT3.1 rat prostatic cells greatly suppresses their metastatic ability to the lungs without suppression of their in vivo growth rate or tumorigenicity. These results suggest that CD44 is a metastasis suppressor for prostatic cancer and that decreased expression of the standard form of CD44 is involved in the progression of prostatic cancer to a metastatic state.
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PMID:CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. 904 Nov 84

The expressions of E-cadherin, the integrin subunits beta 1, beta 2, beta 3, CD44 and alpha-catenin were studied in parallel by immunohistochemistry in a series of 40 prostate biopsies comprising one normal, 11 benign prostatic hyperplasia (BPH), and 28 prostatic adenocarcinomas. As reported by others, there was a consistent loss of E-cadherin expression with increasing tumour grade and de-differentiation. However, a significant proportion of losses occurred at earlier grades than previously reported. The parallel nature of this study showed, for the first time in human prostate carcinoma, a reciprocal expression pattern of E-cadherin and beta 1 integrin in the higher grades of prostate cancer. A reciprocal expression pattern was also found for E-cadherin and CD44 between moderately and poorly differentiated tumours. alpha-Catenin expression was downregulated only in those cells which had previously lost E-cadherin expression, and beta 2 and beta 3 integrin were rarely expressed in prostate tumours. A loss of expression of the luminal epithelial specific keratins CK8 and CK18 was also observed in advanced stage, poorly differentiated carcinomas.
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PMID:Co-ordinated changes in expression of cell adhesion molecules in prostate cancer. 913 98


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