Colorectal Cancer Cell Invasion and Functional Properties Depend on Peri-Tumoral Extracellular Matrix

Author:

Franchi Marco1ORCID,Karamanos Konstantinos-Athanasios2,Cappadone Concettina3ORCID,Calonghi Natalia3,Greco Nicola4,Franchi Leonardo5,Onisto Maurizio4ORCID,Masola Valentina4ORCID

Affiliation:

1. Department for Life Quality Studies, University of Bologna, 47900 Rimini, Italy

2. Department of Pharmacy and Industrial Pharmacy, University of Bologna, 40126 Bologna, Italy

3. Department of Pharmacy and Biotechnologies, University of Bologna, 40126 Bologna, Italy

4. Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy

5. Department of Medicine, University of Bologna, 40126 Bologna, Italy

Abstract

We investigated how the extracellular matrix (ECM) affects LoVo colorectal cancer cells behavior during a spatiotemporal invasion. Epithelial-to-mesenchymal transition (EMT) markers, matrix-degrading enzymes, and morphological phenotypes expressed by LoVo-S (doxorubicin-sensitive) and higher aggressive LoVo-R (doxorubicin-resistant) were evaluated in cells cultured for 3 and 24 h on Millipore filters covered by Matrigel, mimicking the basement membrane, or type I Collagen reproducing a desmoplastic lamina propria. EMT and invasiveness were investigated with RT-qPCR, Western blot, and scanning electron microscopy. As time went by, most gene expressions decreased, but in type I Collagen samples, a strong reduction and high increase in MMP-2 expression in LoVo-S and -R cells occurred, respectively. These data were confirmed by the development of an epithelial morphological phenotype in LoVo-S and invading phenotypes with invadopodia in LoVo-R cells as well as by protein-level analysis. We suggest that the duration of culturing and type of substrate influence the morphological phenotype and aggressiveness of both these cell types differently. In particular, the type I collagen meshwork, consisting of large fibrils confining inter fibrillar micropores, affects the two cell types differently. It attenuates drug-sensitive LoVo-S cell aggressiveness but improves a proteolytic invasion in drug-resistant LoVo-R cells as time goes by. Experimental studies on CRC cells should examine the peri-tumoral ECM components, as well as the dynamic physical conditions of TME, which affect the behavior and aggressiveness of both drug-sensitive and drug-resistant LoVo cells differently.

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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