Integrin alpha2beta1 (α2β1) promotes prostate cancer skeletal metastasis

• Published in: Clinical & experimental metastasis 2013-06, Vol.30 (5), p.569-578
• Main Authors: Sottnik, Joseph L., Daignault-Newton, Stephanie, Zhang, Xiaotun, Morrissey, Colm, Hussain, Maha H., Keller, Evan T., Hall, Christopher L.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Hematology; Oncology; Research Paper; Surgical Oncology
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-012-9561-6

Men who die of prostate cancer (PCa) do so because of systemic metastases, the most frequent of which are within the skeleton. Recent data suggest that the colonization of the skeleton is mediated in part by collagen type I, the most abundant protein within the bone. We have shown that enhanced collagen I binding through increased expression of integrin α 2 β 1 stimulated in vitro invasion and promoted the growth of PCa cells within the bone. Accordingly, we sought to determine whether α 2 β 1 integrin is a potential mediator of skeletal metastasis. To examine whether α 2 β 1 integrin mediates PCa metastasis, α 2 integrin was over-expressed in low-tumorigenic LNCaP PCa cells or selectively knocked-down in highly metastatic LNCaP col PCa cells. We document that the over-expression of α 2 cDNA stimulated whereas α 2 shRNA inhibited the ability of transduced cells to bind to or migrate towards collagen in vitro. Correspondingly, α 2 integrin knock-down reduced the tumor burden of intra-osseous tumors compared to control-transduced cells. To investigate the clinical significance of α 2 β 1 expression in PCa, α 2 β 1 protein was measured in prostatic tissues and in soft tissue and bone metastases. The data demonstrate that α 2 β 1 protein was elevated in PCa skeletal metastases compared to either PCa primary lesions or soft tissue metastases suggesting that α 2 β 1 contributes to the selective metastasis to the bone. Taken together, these data support that α 2 β 1 integrin is needed for the efficient metastasis of PCa cells to the skeleton.