Caught in the act: multiphoton microscopy reveals host extracellular matrix remodeling by a human cancer-avatar model

ABSTRACT: : Cancer cells facilitate tumor growth by creating favorable tumor micro-environments (TME), altering homeostasis and immune response in the extracellular matrix (ECM) of surrounding tissue. A potential factor that contributes to TME generation and ECM remodeling is the cytoskeleton-associated human death-associated protein kinase 1 (DAPK1). Increased tumor cell motility and de-adhesion (thus, promoting metastasis), as well as upregulated plasminogen-signaling are shown when functionally analyzing the DAPK1 ko related proteome. However, the systematic investigation how tumor cells actively modulate the ECM at the tissue level is experimentally challenging, since animal models do not allow direct experimental access while artificial in vitro scaffolds cannot simulate the entire complexity of tissue systems. Here, we used the chorioallantoic membrane (CAM) assay as a natural, collagen-rich tissue model in combination with an all-optical experimental access by multiphoton microscopy (MPM) in order to study the ECM remodeling potential of colorectal tumor cells with and without DAPK1 in situ and even in vivo. This approach demonstrates the suitability of the CAM assay in combination with multiphoton microscopy for studying collagen remodeling during tumor growth. Our results indicate the high ECM remodeling potential of DAPK1 ko tumor cells at the tissue level and support our findings from proteomics.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Karel Harant  

LAB HEAD: Regine Schneider-Stock

PROVIDER: PXD026072 | Pride | 2022-06-09

REPOSITORIES: Pride