Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority of papillary transitional cell carcinomas of the bladder are localized tumors at initial diagnosis; identification of those developing recurrence and an aggressive behavior is important. CD44 variant proteins have been implicated in tumor progression and metastasis, and a correlation with adverse prognosis has been demonstrated in a variety of human tumors. Here, the usefulness of conventional CD44 protein immunohistochemistry as a prognostic parameter for recurrence of superficial transitional cell carcinomas was assessed in paraffin sections of 241 tumors with long-term follow-up. A highly significant association was found between focal loss of CD44v3 and -v6 immunostaining and short recurrence-free interval in noninvasive (pTa) transitional cell carcinomas (P = 0.005), but not in minimally invasive (pT1) carcinomas (P = 0.78). Our results indicate the value of conventional CD44 immunohistochemistry as an additional tool for identifying patients at high risk for recurrence of pTa transitional cell carcinomas. They also point to biological differences between noninvasive and minimally invasive transitional cell carcinomas of the bladder.
 ...
PMID:Focal loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma. 1055 Feb 96

The CD44 variant 6 (CD44 v6) has been postulated to be involved in both carcinogenesis and tumor progression. In the present study, CD44 v6 was stained immunohistochemically in 63 colorectal cancer tissues to assess significance of CD44 v6 in the carcinogenesis and progression of colorectal carcinoma. None of the normal colonocytes showed an expression of CD44 v6. CD44 v6 expression was very strong in 24, moderate in 13, and negative in 26 tumor tissues. A negative or moderate expression of CD44 v6 was significantly associated with a larger tumor size (P < 0.05) and invasion through the bowel wall (P < 0.01). There was no correlation between the expression of CD44 v6 and gross type, histologic differentiation, lymph node involvement, liver metastasis, and clinical stage of the disease. The present study showed that the expression of CD44 v6 was characteristic of neoplastic changes in the colonocytes and that a diminished expression of CD44 v6 was associated with the penetration of colorectal cancer through the bowel wall, but not with either lymph node or distant metastasis.
 ...
PMID:Immunohistochemical expression of the CD44 variant 6 in colorectal adenocarcinoma. 1064 79

Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e., the mesothelium covering the ovary, but experimental evidence for this origin has been lacking. Contrary to most epithelia, where neoplastic progression is associated with a reduction of E-cadherin, this cell-cell adhesion molecule is sparse in normal human OSE but its expression increases with the development of ovarian epithelial metaplasia and neoplasia. Concurrently, the tumors tend to acquire characteristics of the complex epithelia of the oviduct and uterus. The high proportion of ovarian cancers where such aberrant Mullerian differentiation occurs suggests that this change may confer a selective advantage on the transforming cells. We previously demonstrated that increased E-cadherin expression may be a cause, rather than a consequence, of such Mullerian differentiation. E-cadherin was transfected into SV40 large T antigen-immortalized, E-cadherin-negative cells derived from normal OSE. Constitutive expression of E-cadherin re-established normal epithelial markers that had been lost in culture, such as keratin, and induced markers of metaplasia and neoplasia, such as CA125. In the present study, SV40-immortalized, E-cadherin-transfected cells, but not the E-cadherin-negative controls, were found to be anchorage-independent and to form transplantable, invasive s.c. and i.p. adenocarcinomas in 100% of injected SCID mice. Tumor cells injected i.p. seeded the mesenteries and omentum, invaded the liver and thigh musculature and produced ascites. The presence of SV40 large T antigen in the tumor cell nuclei confirmed their origin as transfected OSE cells. Our results demonstrate that ovarian adenocarcinomas can be derived by genetic manipulation of normal human OSE.
 ...
PMID:An ovarian adenocarcinoma line derived from SV40/E-cadherin-transfected normal human ovarian surface epithelium. 1065 37

Changes in cell-cell interactions are critical in the process of cancer progression. Likewise, it has been shown that loss of expression of the cell adhesion molecule E-cadherin is associated with grade, stage, and prognosis in many carcinomas, including prostate cancer. Impaired E-cadherin-mediated interactions result in an invasive phenotype; however, the mere loss of cell-cell contact and communication is not the sole explanation for the observed correlation between loss of E-cadherin-mediated adhesion and poor clinical outcome. Using a degenerate cloning strategy for sequences that are highly conserved between the various cadherins, we found several other cadherins (N- and P-cadherin and cadherin-4, -6, and -11) to be expressed in human prostate cancer cells. Our data suggest that besides loss of E-cadherin function, also (upregulation of) expression of other cadherins is involved in the acquisition of an invasive and/or metastatic phenotype. Especially, changes in the expression of N-cadherin and cadherin-11 may play an important role in prostate cancer progression.
 ...
PMID:Complex cadherin expression in human prostate cancer cells. 1065 39

Migration of some tumor cells, and their lodgment in target organs, is dependent on the activation of cell surface CD44 receptor, usually detected by its ability to bind hyaluronic acid (HA) or other ligands. In an attempt to reveal the mechanism of tumor cell CD44 activation, we compared the physical and chemical properties of CD44 in nonactivated LB cell lymphoma with those in phorbol 12-myristate 13-acetate (PMA)-activated LB cells and of an LB cell subline (designated HA9) expressing constitutively-active CD44. In contrast to nonactivated LB cells, PMA-activated LB cells and HA9 cells displayed a CD44-dependent ability to bind HA. The ability of activated cell CD44 to bind HA was not dependent on microfilament or microtubule integrity or on changes in CD44 mobility on the membrane plane, indicating that the CD44 activation status is not associated with cytoskeleton function. Aside from the increased expression of CD44 on the surface of PMA-activated LB cells and HA9 cells, qualitative differences between the CD44 of nonactivated and activated LB cells were also detected: the CD44 of the activated lymphoma was (i) larger in molecular size, (ii) displayed a broader CD44 isoform repertoire, including a CD44 variant that binds HA, and (iii) its glycoprotein contained less sialic acid. Indeed, after removal of sialic acid from their cell surface by neuraminidase, LB cells acquired the ability to bind HA. However, a reduced dose of neuraminidase did not confer HA binding on LB cells, unless they were also activated by a low concentration of PMA, which by itself was ineffective. Similarly, under suboptimal conditions, a synergistic effect was obtained with tunicamycin and PMA: each one alone was ineffective but in combination they induced the acquisition of HA binding by the lymphoma cells, while their CD44 expression was not enhanced. Unveiling of the activation mechanism of CD44, by exposing the cells to PMA stimulation or to deglycosylation, is not only academically important, but it also has practical implications, as activated CD44 may be involved in the support of tumor progression.
 ...
PMID:The CD44 receptor of lymphoma cells: structure-function relationships and mechanism of activation. 1071 94

E-cadherin is the main cell adhesion molecule of early embryonic and adult epithelial cells. Downregulation of E-cadherin is associated with epithelial-mesenchymal transition during embryonic mesoderm formation and tumor progression. To identify genes whose expression is affected by the loss of E-cadherin, we compared mRNA expression patterns between wild-type and E-cadherin null mutant embryonic stem (ES) cells. We found that expression of several Eph receptors and ephrins is dependent on E-cadherin. Rescue of E-cadherin null ES cells with E-cadherin cDNA restores the wild-type expression pattern of Eph family members. Rescue of E-cadherin null ES cells with N-cadherin cDNA does not restore the wild-type expression pattern, indicating that the regulation of differential expression of Eph family members is specific to E-cadherin. Constitutive ectopic expression of E-cadherin in non-epithelial NIH3T3 cells results in the production of the EphA2 receptor. In epithelial cells, E-cadherin is required for EphA2 receptor localization at cell-cell contacts; in the absence of functional E-cadherin, EphA2 localizes to the perinuclear region. Our results indicate that E-cadherin may be directly or indirectly required for the membrane localization of Eph receptors and their membrane-bound ligands.
 ...
PMID:Expression of Eph receptors and ephrins is differentially regulated by E-cadherin. 1076 10

Regulation of alternative pre-mRNA splicing, recognized as increasingly important in causing human disease, was studied using the CD44 gene, whose splice variants have been implicated in tumor progression. We identified heterogeneous ribonucleoprotein (hnRNP) A1 as a protein interacting in vitro and in vivo with regulatory splice elements in CD44 variant exon v5. Transient overexpression of hnRNP A1 prevented v5 exon inclusion, dependent on the exonic elements. HnRNP A1-dependent repression was exon-specific and could be relieved by coexpression of oncogenic forms of Ras and Cdc42. The results define hnRNP A1 as a decisive part of an oncogene-regulated splice-silencing complex, which can select between multiple alternatively spliced exons.
 ...
PMID:Heterogeneous ribonucleoprotein A1 is part of an exon-specific splice-silencing complex controlled by oncogenic signaling pathways. 1095 93

Interactions of hyaluronic acid (HA) with its binding proteins CD44 and RHAMM (receptor for HA-mediating motility) have been proposed to be important in promoting tumor progression and dissemination. However, a comparative study of their expression patterns in stomach cancer and its associated lesions is not yet available. To address this issue, the combined examinations of pathology, immunocytochemistry and Western blot hybridization were performed on advanced gastric cancer specimens as well as their preneoplastic and non-cancerous counterparts. Alternative CD44 expression was observed in the gastric mucosa with different lesions. CD44 proteins harboring variant exon 6 (CD44 v6) was detected only in cancer tissues with a total positive rate of 14% (10/74). Intracellular RHAMM molecules in Mr 93000 to 95000 were expressed in 3/31 non-cancerous mucosa. RHAMM detection rates increased along with tumor progression. Irrespective of the differences of gross and morphological pattern, majority (54/74) of cancer cases expressed multiple RHAMM isoforms in Mr 40000-45000, 64000, 70000-73000, 85000 and 93000-95000 with the appearance of cell surface immunocytochemical labeling. Among CD44 variant isoforms, v6 is more relevant with malignant transformation of gastric epithelium. Expression of RHAMM, especially the cell surface variants, is closely correlated with tumor progression (P<0.01). Expression of CD44 and RHAMM may benefit the invasion and metastasis of gastric cancer cells presumably in a reciprocal manner.
 ...
PMID:Expression of hyaluronan receptors CD44 and RHAMM in stomach cancers: relevance with tumor progression. 1102 94

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing of messenger RNA. These splice variants have been shown in several cancer cell types and are thought to be involved in tumor progression. The aim of the current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other markers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal antibodies: anti-CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cells were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 variants tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms varied, depending on lung cancer histology. In general, CD44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 cases with metastases, tumor cells had high v6 and Ki-67 expression, but these data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in anaplastic small cell or large cell cancers only v10 expression seems to correlate with proteins associated with tumor growth and progression.
 ...
PMID:Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer. 1105 26

Basal-cell adhesion molecule (B-CAM) is a 90 kDa cell surface glycoprotein of the immunoglobulin superfamily that functions as a laminin-binding receptor. B-CAM is upregulated following malignant transformation of some cell types in vivo and in vitro, thus being a candidate molecule involved in tumor progression. As cutaneous distribution and function of B-CAM are largely unknown, we have studied its expression and regulation in normal and diseased human skin. In normal skin, B-CAM was expressed by endothelial cells of dermal blood vessels. In contrast, B-CAM was strongly upregulated within the tumor tissue of both malignant and benign epithelial skin tumors, including basal cell carcinomas, squamous cell carcinomas, keratoacanthomas, and common warts. Transformation-associated upregulation was confirmed in vitro, but normal keratinocytes also expressed B-CAM under culture conditions. Interestingly, the basal epidermal layer of normal-appearing skin surrounding the tumors also expressed B-CAM, and B-CAM were induced on the basal and apicolateral surfaces of basal keratinocytes in inflammatory skin disorders suggesting transformation-independent mechanisms of epidermal induction of the B-CAM. Immunoelectron microscopy studies of cultured transformed keratinocytes revealed that B-CAM was expressed at cell-cell and cell-substrate contact sites. Halting proliferation of transformed keratinocytes through cytostatic drugs resulted in decreased B-CAM synthesis. Likewise, inducing terminal differentiation in keratinocyte cultures by increasing the Ca(2+) concentration in the medium decreased B-CAM expression. In contrast, both ultraviolet A and B irradiation of cultured human keratinocytes resulted in significantly increased expression of the B-CAM. Overall, it appears that B-CAM expression in human skin is associated with activated states of keratinocytes, and that B-CAM may be involved in cell-cell adhesion or migration, in addition to its known function as a laminin receptor. J Invest Dermatol 115:1047-1053 2000
 ...
PMID:Basal-cell adhesion molecule (B-CAM) is induced in epithelial skin tumors and inflammatory epidermis, and is expressed at cell-cell and cell-substrate contact sites. 1167 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>