TY - JOUR
T1 - Osteopontin stimulates preneoplastic cellular proliferation through activation of the MAPK pathway
AU - Luo, Xianmin
AU - Ruhland, Megan K.
AU - Pazolli, Ermira
AU - Lind, Anne C.
AU - Stewart, Sheila A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80051985501&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-10-0472
DO - 10.1158/1541-7786.MCR-10-0472
M3 - Article
C2 - 21673011
AN - SCOPUS:80051985501
VL - 9
SP - 1018
EP - 1029
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 8
ER -