Hypoxia favors tumor growth in colorectal cancer in an integrin αDβ1/hemoglobin δ-dependent manner

Low oxygen tension (PO2), characterizes the tissue environment of tumors. The colorectal tumor line Colo205, grown under reduced oxygen tension expresses a novel αDβ1 integrin, which forms a cell surface complex with hemoglobin δ. This resulted in high local affinity for oxygen, which increased cell adhesion as compared with cells grown under normal oxygen tension. Staining with antibodies to the integrin αD polypeptide and hemoglobin δ, and transfection with cDNAs for GFP-hemoglobin δ and mCherry-αD, showed co-localization of αD and hemoglobin δ. Antibodies to αD and β1 integrins, an RGD peptide, and an αDβ1 binding peptide from hemoglobin δ, blocked the αDβ1-hemoglobin interaction and lowered oxygen consumption. Downregulation of integrin αD or hemoglobin δ expression inhibited cell proliferation in hypoxia. The very frequent expression of complexes between αDβ1 and hemoglobin δ on the cell surface offers potential diagnostic and therapeutic targets in colorectal cancer.All data including the Trihalo protein stains of gels, uncropped and unprocessed images of all immunoblots, and histochemical array stains of patient samples will be archived in a permanent repository (See supplementary information). The experimental data and the results that support the findings of this study will then be available in the repository. The Public Data Base access is (https://portal.gdc.cancer.gov/).Ethical approvalTissue archived sample examinations were performed with permission from the Finnish Medicines Agency Dnro FIMEA/2021/006901. The Surgical Ethics Committee of Helsinki approved the study protocol (permit 226/E6/06, extension TKM02). The consent of the patients were obtained.