Increased gene expression levels of collagen receptor integrins are associated with decreased survival parameters in patients with advanced melanoma

Vuoristo, Mikko; Vihinen, Pia; Vlaykova, Tatyana; Nylund, C. E.; Heino, Jyrki; Pyrhönen, Seppo

doi:10.1097/cmr.0b013e328270b935

Cited by 21 publications

(21 citation statements)

References 35 publications

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“…Western blot results showed that expression of ANGPTL1 inversely correlated with p-ERK expression (Supplemental Figure 12, A and B). Two important collagen receptors, integrin α 1 β 1 and integrin α 2 β 1 , have been shown to correlate with cell invasiveness and metastasis (35)(36)(37)(38)(39). To evaluate whether integrin α 1 β 1 is involved in ANGPTL1-regulated cell motility and invasiveness and SLUG expression, we first investigated the expression of integrin α 1 β 1 and integrin α 2 β 1 using RT-PCR.…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility

Kuo¹,

Tan²,

Chang³

et al. 2013

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 99%

Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility

Kuo¹,

Tan²,

Chang³

et al. 2013

J. Clin. Invest.

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“…However, at the protein level, α 2 β 1 is readily detected at both primary and metastatic sites in a variety of cancers, including breast (as described herein) and prostate cancer (52,55,56). Although it may be reasonable to conclude that high levels of α 2 β 1 can potentially retard motile responses by promoting adhesion, lower levels of the integrin nevertheless may be required to support the cell-ECM interactions most conducive to invasion and growth.…”

Section: Discussionmentioning

confidence: 97%

A 3D matrix platform for the rapid generation of therapeutic anti-human carcinoma monoclonal antibodies

Dudley¹,

Li²,

Hu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Efforts to develop unbiased screens for identifying novel functionblocking monoclonal antibodies (mAbs) in human carcinomatous states have been hampered by the limited ability to design in vitro models that recapitulate tumor cell behavior in vivo. Given that only invasive carcinoma cells gain permanent access to type I collagen-rich interstitial tissues, an experimental platform was established in which human breast cancer cells were embedded in 3D aldimine cross-linked collagen matrices and used as an immunogen to generate mAb libraries. In turn, cancer-cell-reactive antibodies were screened for their ability to block carcinoma cell proliferation within collagen hydrogels that mimic the in vivo environment. As a proof of principle, a single function-blocking mAb out of 15 identified was selected for further analysis and found to be capable of halting carcinoma cell proliferation, inducing apoptosis, and exerting global changes in gene expression in vitro. The ability of this mAb to block carcinoma cell proliferation and metastatic activity was confirmed in vivo, and the target antigen was identified by mass spectroscopy as the α 2 subunit of the α 2 β 1 integrin, one of the major type I collagen-binding receptors in mammalian cells. Validating the ability of the in vitro model to predict patterns of antigen expression in the disease setting, immunohistochemical analyses of tissues from patients with breast cancer verified markedly increased expression of the α 2 subunit in vivo. These results not only highlight the utility of this discovery platform for rapidly selecting and characterizing function-blocking, anticancer mAbs in an unbiased fashion, but also identify α 2 β 1 as a potential target in human carcinomatous states.n mammalian systems, a specialized form of extracellular matrix (ECM), termed the basement membrane, normally separates epithelial cells from the underlying type I collagen-rich interstitial matrix (1, 2). Thus, in mature animals and under physiologic conditions, the epithelium does not establish stable physical contacts with interstitial tissues (1, 2). In contrast, in neoplastic states, transformed epithelial cells (i.e., carcinomas) dissolve the intervening basement membrane barrier and establish adhesive interactions with the newly exposed type I collagen fibrillar network (1-5). As carcinoma cells begin to infiltrate the interstitial matrix, they rapidly adapt themselves to their 3D environment and initiate the proliferative phenotypes that define tumor progression at both primary and metastatic sites (2, 6, 7). Indeed, emphasizing the importance of the tumor-ECM interface, carcinoma cells do not simply use the surrounding interstitial matrix as a passive substrate, but actively promote increased type I collagen deposition within the peritumoral microenvironment as a means of further enhancing invasive activity, local growth, and cancer stem cell formation (7-12).Despite the importance of the carcinoma cell-type I collagen interface in vivo, therapeutic interventions that directly inte...

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“…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.…”

Section: Figmentioning

confidence: 97%

“…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). The NG2 has been reported to be an invasive marker in gliomas (Wiranowska et al 2006) and has been found to enhance the growth and metastatic properties of melanoma cells (Burg et al 1998).…”

Section: Introductionmentioning

confidence: 98%

Prominent collagen type VI expression in juvenile angiofibromas

Gramann

Wendler

Haeberle³

et al. 2008

Histochem Cell Biol

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The extracellular matrix component collagen type VI demonstrates potent growth-stimulatory effects and has been associated with aggressive tumour growth. Although, juvenile angiofibromas (JAs) often exhibit an aggressive growth pattern, the collagen type VI expression of this fibrovascular tumour has not been addressed so far. RT-PCR, Western blot analysis and immunohistochemistry were used in this study to analyse collagen type VI, type VI collagen receptor subunits (integrin alpha1, alpha2, alpha10, alpha11 and beta1) and the type VI collagen receptor NG2 in JAs (N = 15) and nasal mucosa (NM, N = 8) samples. The mRNA expression of all three collagen type VI chains was found to be up-regulated significantly (P < 10(-3)-10(-5), adjusted) in JAs compared to NM tissues. The Western blot analysis proved highly prominent collagen-type VI expression in JAs. The ApoTome technique revealed strong collagen-type VI signals in tumour endothelium. NG2 (P < 10(-3), adjusted) and alpha11-integrin (P = 0.04, adjusted) showed a significantly higher mRNA expression levels in JAs than in NM samples. NG2, alpha1-, alpha2- and beta1-intergin were located to tumour vessels, and additional stromal signals were observed for NG2 and alpha1-integrin in JAs. This study demonstrates a prominent collagen-type VI expression in JAs. The collagen-type VI may exert an important growth stimulus in this tumour.

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Increased gene expression levels of collagen receptor integrins are associated with decreased survival parameters in patients with advanced melanoma

Cited by 21 publications

References 35 publications

Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility

Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility

A 3D matrix platform for the rapid generation of therapeutic anti-human carcinoma monoclonal antibodies

Prominent collagen type VI expression in juvenile angiofibromas

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