Regulation of prostate cell collagen receptors by malignant transformation

Abstract

Cell adhesion receptors, including the integrin-type collagen receptors (a 1 b 1 , a 2 b 1 , a 10 b 1 and a 11 b 1 ) participate in cancer progression and invasion. Quantitative RT-PCR indicated that all 4 receptors are abundantly expressed in sarcoma-derived cell lines, whereas most carcinoma-derived cells express a 1 b 1 and a 2 b 1 only. This was surprising because a 11 b 1 has been connected previously to the progression of lung adenocarcinomas. To test the hypothesis that a 11 expression may not persist in cultured cancer cells we analyzed fresh tissue samples of 104 total prostatectomies, keeping in mind that prostate cancer cell lines showed negligible a 11 mRNA levels. In prostate a 2 expression was significantly lower in poorly differentiated carcinomas when compared to benign lesions (p 5 0.0331). In immunohistochemistry the protein levels of a 2 integrin decreased significantly (p 5 0.0001) and the protein levels of a 11 subunit increased significantly (p 5 0.029) with the increasing grade of carcinoma. Thus a 11 b 1 may replace a 2 b 1 during tumor progression. Our observations support the idea that a 11 b 1 may be expressed in tumors but the corresponding cell lines may lose the expression of this integrin. Previous studies have shown that in cell culture androgen receptor (AR) controls a 2 b 1 expression. We measured AR mRNA levels and the number of AR positive nuclei in the prostate samples and the results showed a significant correlation between a 2 b 1 and AR. Androgen receptors may control the mechanisms regulating integrin expression in prostate. ' 2005 Wiley-Liss, Inc.Key words: integrins; collagen; prostate; cancer; cell linesIntegrins are adhesion molecules that act in cell-cell and cellextracellular matrix interactions. They comprise of 2 subunits called a and b, which can form at least 24 different non-covalently linked a/b-heterodimers.1 Four collagen receptors form a specific subclass of integrins because they all contain an inserted domain (I domain) in their a subunit. These a subunits form heterodimers with b 1 subunit only.The most abundant integrin-type collagen receptors are a 1 b 1 and a 2 b 1 . Integrin a 1 b 1 is predominantly expressed in mesenchyme and the highest expression levels are on smooth muscle cells.2,3 Integrin a 2 b 1 is expressed abundantly on epithelial cells but it is also present on many mesenchymal cells, such as fibroblasts, chondrocytes and osteoblasts. [4][5][6] The newest members of the collagen receptor integrins, a 10 b 1 and a 11 b 1 , were found more recently 7,8 and their expression patterns are less well-known. 9,10Integrins have been shown to regulate cell growth, differentiation and survival, as well as malignant transformation, cancer cell invasion and metastasis.11 When malignant tumors and cancer cells have been analyzed, the expression and function of a 2 b 1 has been connected to invasion of malignant melanoma 12 as well as to prostatic, gastric and ovarian carcinomas, 13-15 whereas a 1 b 1 integrin is the collagen receptor of T cell derived ...

Activation of the α2β1 integrin‐mediated malignant phenotype on type I collagen in pancreatic cancer cells by shifts in the concentrations of extracellular Mg2+ and Ca2+

“…43,44 And third, recent quantitative RT-PCR analyses of cancer cell lines for collagen receptor expression indicate that a 1 b 1 , a 2 b 1 , a 10 b 1 and a 11 b 1 are abundantly expressed in sarcomaderived cell lines, whereas most carcinoma-derived cell lines express only the a 1 b 1 and a 2 b 1 integrins. 50 However, pancreatic adenocarcinoma cell lines were not investigated in that study. Together with the known affinity differences of the monoclonal antibodies used in these and our previous studies, 20,26,27,[39][40][41] where the b 1 antibody has a higher affinity than the a 2 antibody, these data collectively suggest that only the a 2 b 1 integrin is involved in pancreatic cancer cell interactions with Type I collagen.…”

Integrins as Determinants of Genetic Susceptibility, Tumour Behaviour and Their Potential as Therapeutic Targets

“…For example, studies of primary and metastatic prostate carcinomas have reported that α 2 β 1 expression is down-regulated in low grade tumours, heterozygous in intermediate grades, and up-regulated in lymph node metastases (Bonkhoff et al, 1993;Knox et al, 1994;Kostenuik et al 1996). Mirtti et al, (2006) have reported differential expression levels in prostate tumour cell lines, and lower α 2 mRNA and protein expression in higher grade tumours when compared to benign lesions, although the levels of mRNA expression reported by Mirtti et al (2006) again varied widely in tumours. Moreover, α 6 expression has been shown to be up-regulated in metastases and adenocarcinoma (Bonkhoff et al, 1993;Knox et al, 1994;Nagle et al, 1995;Schmelz et al, 2002), whereas α 2 has been shown to be down-regulated in adenocarcinomas and up-regulated in metastatic tumours (Bonkhoff et al, 1993;Nagle et al, 1995).…”

Prominent collagen type VI expression in juvenile angiofibromas

“…Low collagen type II, 10-and 11-integrin mRNA levels in JAs in our studies are in line with negation of tumour origin from cartilage tissue. 11-integrin is reported to be associated with decreased survival parameters in melanomas (Vuoristo et al 2007) and progression of lung adenocarcinomas (Mirtti et al 2006). Here, we noted a statistically signiWcant up-regulation of 11-integrin mRNA in JAs compared to NM tissues.…”

“…It has been suggested that integrin receptor expression is regulated by transforming growth factor-(TGF-) (Heino 2000) and is correlated to androgen receptor (AR) expression level (Mirtti et al 2006). Both TGF-and AR have already been described in JAs and are thought to be involved in tumour biology (Schick and Urbschat 2004).…”

“…While all four integrin-type collagen receptors are abundantly expressed in sarcoma-derived cell lines, most carcinoma-derived cells express only 1 1-and 2 1-integrin (Mirtti et al 2006). In advanced melanomas increased 1-, 2-and 11-integrin mRNA levels were reported to be associated with decreased survival parameters (Vuoristo et al 2007).…”