Calcineurin Inhibitors Promote Metastasis in Post-Transplant Colorectal Cancer Through Cancer Related- Exosomes Released from Cancer Cells in TGF Beta Independent Epitheilal to Mesenquimal Transition.
1Experimental Laboratory of Nephrology and Kidney Transplant, IDIBAPS, Barcelona, Spain
2Department of Nephrology and Kidney Transplant, Hospital Clínic, Barcelona, Spain
3Dipartamento di Epidemiologia e Ricerca Pre-Clinica, INMI “L. Spallanzani&rdquo
IRCCC, Rome, Italy
4ISGlobal, CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
5National Network for Kidney Research (REDinREN), Carlos III Royal Institute, Ministry of Health, Madrid, Spain
6IRCCS Centro di Riferimento Oncologico, Aviano, Italy
7Institució
Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Meeting: 2016 American Transplant Congress
Abstract number: A39
Keywords: Calcineurin, Kidney transplantation, Post-transplant malignancy, Transforming growth factor-beta (TGF-b)
Session Information
Date: Saturday, June 11, 2016
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
Introduction: Cancer is one of the major causes of death in kidney transplantation. Despite more mortality in colon cancer (CRC), similar incidence than general population is known. CRC characterization by our group showed differences in cancer behaviour without significant differences in mTOR and TGF-B expression patterns associated to the immunosuppressive therapy. Our aim is to evaluate the mechanism of metastasis of cyclosporine (Csa) comparing rapamycin (RAPA) in CRC.
Method: Non- metastatic (SW480) and metastatic (HCT 116) CRC cell lines were treated with Csa (10 [mu]M), RAPA (20nM), and TGF-β (5 ng/ml). Proliferation and viability assays (CyQuant; MTT), and gene (qPCR), protein (WB; IF) expression of EMT (CK8;Snail,Vimentin) were analyzed. Cancer-exosome (CaEx) isolation was done by ultracentrifugation, and quantification by nanosight.
Results: Csa produced more proliferation than RAPA in SW480 and HCT 116 (97,3vs66,36 ng/ml; 120,85vs84,68ng/ml; p<0.05), with same viability at 24h (p=0.05). CK8 gene and protein expression were lower in Csa-SW480 than SRL-SW480, and higher Snail and Vimentin gene and protein expression in Csa-HCT116. CaEx production was higher in Csa-SW480 and Csa-HCT116 than RAPA (2.59*109 vs 8.21*108 particules/ml) three times higher in Csa-treated cells adjusting by number of CaEx per cell (1.726,7*105 vs 547.3*105; p<0.05). TGF-β treatment did not show differences in proliferation, viability, molecular expression, and CaEx release due to the mutations in TGF-β pathway in these cells.
Conclusion: Csa treatment produces more cell proliferation and induction of TGF-β independent- EMT than RAPA in metastatic CRC cell lines by higher CaEx release.
CITATION INFORMATION: Tubita V, Segui-Barber J, Ramírez-Bajo M.-J, Moya-Rull D, Piselli P, Verdirosi D, Oppenheimer F, Serraino D, Del Portillo H, Diekmann F, Campistol J, Revuelta I. Calcineurin Inhibitors Promote Metastasis in Post-Transplant Colorectal Cancer Through Cancer Related- Exosomes Released from Cancer Cells in TGF Beta Independent Epitheilal to Mesenquimal Transition. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Tubita V, Segui-Barber J, Ramírez-Bajo M-J, Moya-Rull D, Piselli P, Verdirosi D, Oppenheimer F, Serraino D, Portillo HDel, Diekmann F, Campistol J, Revuelta I. Calcineurin Inhibitors Promote Metastasis in Post-Transplant Colorectal Cancer Through Cancer Related- Exosomes Released from Cancer Cells in TGF Beta Independent Epitheilal to Mesenquimal Transition. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/calcineurin-inhibitors-promote-metastasis-in-post-transplant-colorectal-cancer-through-cancer-related-exosomes-released-from-cancer-cells-in-tgf-beta-independent-epitheilal-to-mesenquimal-transition/. Accessed June 6, 2020.« Back to 2016 American Transplant Congress