Osteopontin stimulates preneoplastic cellular proliferation through activation of the MAPK pathway

Xianmin Luo, Megan K. Ruhland, Ermira Pazolli, Anne C. Lind, Sheila A. Stewart

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Alterations in the microenvironment collaborate with cell autonomous mutations during the transformation process. Indeed, cancer-associated fibroblasts 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 showed that senescence-associated stromal-derived osteopontin 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 to squamous cell carcinoma revealed they express osteopontin. Given the stromal expression of osteopontin, we investigated how osteopontin impacts preneoplastic cell growth. We show that osteopontin 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 osteopontin impacts tumorigenesis by stimulating preneoplastic cell proliferation thus allowing expansion of initiated cells in early lesions.

Original languageEnglish
Pages (from-to)1018-1029
Number of pages12
JournalMolecular Cancer Research
Volume9
Issue number8
DOIs
StatePublished - Aug 2011

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