Figure 5. Invasive Metastatic Skin Tumors Correlate with Increased Integrin, FAK, Src, and MAPK Activities.
(A) DMBA treatment of mice revealed a marked increase in DMBA-induced tumor formation in the absence of TβRII.
(B) Lung metastasis from TβRII-cKO mouse topically treated with DMBA to induce backskin SQCCs. Note typical keratinized SQCC histology as revealed by hematoxylin and eosin staining and K14 immunohistochemistry.
(C–F) Anti-FAK and p-FAK immunohistochemistry on sections from WT anal canal (C), cKO pretumor and tumor stage of anogenital skin (D and E), and cKO-Ras backskin SQCC (F). Str, stroma; Epi, epidermis; Der, dermis.
(G–I) Immunoblots of protein lysates from MKs grown in the presence or absence of serum, ±4 min serum stimulation where indicated. Note: Src activity was assessed by immunoprecipitation/immunoblot analysis using Src and pY417-Src antibodies.
(J–M) Immunofluorescence with antibodies against β1- and active β1-integrin (Ac-β1) performed on tissue sections as indicated.
(N) Quantitative FACS analysis of KO (red) versus WT (blue) cultured MKs with antibodies against the cell surface integrins indicated. Gray lines depict secondary antibody-only control.