Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells

Version 1 : Received: 25 June 2022 / Approved: 12 July 2022 / Online: 12 July 2022 (09:11:05 CEST)

A peer-reviewed article of this Preprint also exists.

Signorelli, R.; Giret, T.M.; Umland, O.; Hadisurya, M.; Lavania, S.; Charles Richard, J.L.; Middleton, A.; Boone, M.M.; Ergonul, A.B.; Tao, W.A.; Amirian, H.; Iliuk, A.; Khan, A.; Diaz, R.; Cortes, D.B.; Garcia-Buitrago, M.; Charles Jacob, H.K. ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells. Biomedicines 2022, 10, 1983. Signorelli, R.; Giret, T.M.; Umland, O.; Hadisurya, M.; Lavania, S.; Charles Richard, J.L.; Middleton, A.; Boone, M.M.; Ergonul, A.B.; Tao, W.A.; Amirian, H.; Iliuk, A.; Khan, A.; Diaz, R.; Cortes, D.B.; Garcia-Buitrago, M.; Charles Jacob, H.K. ALCAM: A Novel Surface Marker on EpCAMlow Circulating Tumor Cells. Biomedicines 2022, 10, 1983.

Abstract

Background: Current strategies in circulating tumor cell (CTC) isolation in pancreatic cancer heavily rely on the EpCAM and cytokeratin cell status. EpCAM is generally not considered as a good marker given its transitory change during Epithelial to Mesenchymal Transition (EMT) or reverse EMT. There is a need to identify other surface markers to capture the complete repertoire of PDAC CTCs. The primary objective of the study is to characterize alternate surface bi-omarkers to EpCAM on CTCs that express low or negligible levels of surface EpCAM in pancre-atic cancer patients. Methods: Flow cytometry and surface mass spectrometry were used to iden-tify proteins expressed on the surface of PDAC CTCs in culture. CTCs were grown under condi-tions of attachment and in co-culture with naïve neutrophils. Putative biomarkers were then validated in GEMMs and patient samples. Results: Surface proteomic profiling of CTCs identi-fied several novel protein biomarkers. ALCAM was identified as a novel robust marker in GEMM models and in patient samples. Conclusions: We identified several novel surface bi-omarkers on CTCs expressed under differing conditions of culture. ALCAM was validated and identified as a novel alternate surface marker on EpCAMlow CTCs.

Keywords

Biomarkers; Pancreatic Cancer; CTC; Surfaceome; Protemics; Flow Cytometry; ALCAM

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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