MS1-1: Imaging Cancer Invasion In Vivo: Mechanisms and Implications for Therapy.

Abstract

Abstract The tumor microenvironment contributes to cancer invasion, growth and survival and thereby impacts tumor responses to therapy. Using infrared-excited multiphoton microscopy in orthotopic fibrosarcoma and melanoma xenografts, we here identify a novel radio- and chemoresistance niche consisting of invading tumor cell strands consisting of several hundred connected cells located within collagen-rich stroma nearby blood and lymph vessels. Despite normoxia, perivascular invasion strands were resistant to high-dose hypofractionated irradiation which otherwise was sufficient to induce regression of the tumor main mass. This invasion-associated chemo-and radioresistance was sensitive to the simultaneous inhibition of β1 and β3 integrins by RNA interference or combined anti-β1/aV integrin antibody treatment leading to proliferation arrest, anoikis induction and subtotal to complete regression of both tumor lesion and invasion strands. Thus, collective invasion is an important invasion mode in solid tumors into a microenvironmentally priviledged perivascular survival niche which conveys radioresistance by integrin-dependent signals. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS1-1.