Matrix Stiffening and EGFR Cooperate to Promote the Collective Invasion of Cancer Cells.

Autor: Grasset EM; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Bertero T; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Bozec A; Face and Neck University Institute, Nice, France.; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Friard J; University Cote d'Azur, CNRS-UMR7370, LP2M, LABEX ICST, Medical School, Nice, France., Bourget I; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Pisano S; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Lecacheur M; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Maiel M; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Bailleux C; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Emelyanov A; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Ilie M; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Hofman P; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Meneguzzi G; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France., Duranton C; University Cote d'Azur, CNRS-UMR7370, LP2M, LABEX ICST, Medical School, Nice, France., Bulavin DV; University Cote d'Azur, CAL, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), FHU OncoAge, CAL, Nice, France., Gaggioli C; University Cote d'Azur, INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), Medical School, Nice, France. gaggioli@unice.fr.
Jazyk: angličtina
Zdroj: Cancer research [Cancer Res] 2018 Sep 15; Vol. 78 (18), pp. 5229-5242. Date of Electronic Publication: 2018 Jul 19.
DOI: 10.1158/0008-5472.CAN-18-0601
Abstrakt: In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here, we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca 2+ ) was a potent intracellular second messenger that drove actomyosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca 2+ through Ca V 1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca 2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche. Significance: This work demonstrates that calcium channels blockers verapamil and diltiazem inhibit mechano-sensitization of EGF-dependent cancer cell collective invasion, introducing potential clinical strategies against stromal-dependent collective invasion. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5229/F1.large.jpg Cancer Res; 78(18); 5229-42. ©2018 AACR .
(©2018 American Association for Cancer Research.)
Databáze: MEDLINE
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