Loss of Laminin a3 induces cell invasion and macrophage infiltration in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a common cancer which invades into dermis through the basement membrane. Laminins are basement membrane proteins which are copiously secreted by SCC keratinocytes. Here we provide evidence using in vitro and in vivo 3D models as well as human tumors that the loss of the laminin a3 chain observed in poorly differentiated cSCC increases tumor invasion with an amoeboid phenotype. There is an increase in recruitment and differentiation of TAMs around invading tumor with a shift towards M2 TAMs. These data provide evidence that loss of the laminin a3 chain in cSCC has an effect on both the epithelial and immune components of cSCC resulting in an aggressive tumor microenvironment. Overall design: RNASeq Analysis of SCCIC1 cell line with shRNA mediated knockdown of LAMA3, LAMB3, LMC2 and SHc control