Osteopontin stimulates preneoplastic cellular proliferation through activation of the MAPK pathway.
Osteopontin stimulates preneoplastic cellular proliferation through activation of the MAPK pathway.
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DOI：
10.1158/1541-7786.mcr-10-0472
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Stewart SA
中科院分区：
文献类型：
--
作者：
Luo X;Ruhland MK;Pazolli E;Lind AC;Stewart SA
Alterations in the microenvironment collaborate with cell autonomous mutations during the transformation process. Indeed, cancer- associated fibroblasts (CAF) and senescent fibroblasts stimulate tumorigenesis in xenograft models. Because senescent fibroblasts accumulate with age, these findings suggest that they contribute to age-related increases in tumorigenesis. Previously we demonstrated that senescent-associated stromal derived osteopontin (OPN) contributes to preneoplastic cell growth in vitro and in xenografts, suggesting that it impacts neoplastic progression. Analysis of fibroblasts within premalignant and malignant skin lesions ranging from solar/actinic keratosis (AK) to squamous cell carcinoma (SCC) revealed they express OPN. Given the stromal expression of OPN, we investigated how OPN impacts preneoplastic cell growth. We demonstrate that OPN promotes preneoplastic keratinocyte cellular proliferation and cell survival through the CD44 cell receptor and activation of the MAPK pathway. These data suggest that stromal-derived OPN impacts tumorigenesis by stimulating preneoplastic cell proliferation thus allowing expansion of initiated cells in early lesions.
