Angiogenin and the MMP9‐TIMP2 axis are up‐regulated in proangiogenic, decidual NK‐like cells from patients with colorectal cancer

• DOI: 10.1096/fj.201701103r
• Publication Date: 2018-05-15T20:22:51Z
• Authors: Antonino Bruno; Barbara Bassani; Davide Giuseppe D...; Ilvana Pitaku; Elisa Cassinotti; Giuseppe Pelosi; Luigi Boni; Lorenzo Dominioni; Douglas M. Noonan; Lorenzo Mortara; Adriana Albini
• Keywords: Angiogenin; MMP9

NK cells are effector lymphocytes involved in tumor immunosurveillance; however, patients with solid malignancies, have compromised functions. We previously reported that lung tumor-associated (TANKs; peripheral blood) and tumor-infiltrating (TINKs) show proangiogenic, decidual NK-like (dNK) phenotype. In this study, we functionally molecularly investigated TINKs TANKs from blood tissue samples of colorectal cancer (CRC), a neoplasm which inflammation angiogenesis clinical relevance, compared them to controls nononcologic inflammatory bowel disease. CRC TINKs/TANKs showed decreased expression for the activatory marker NKG2D, impaired degranulation activity, decidual-like polarization toward CD56brightCD16dim/−CD9+CD49+ subset. secreted cytokines proangiogenic activities, induce endothelial cell proliferation, migration, adhesion, formation capillary-like structures vitro. dNK release specific factors; among which, angiogenin invasion-associated enzymes related MMP9-TIMP1/2 axis. Here, describe, first time, our knowledge, angiogenin, MMP2/9, TIMP by CRC. This phenotype could be relevant invasive capabilities functions CRC-NK become novel biomarker. STAT3/STAT5 activation was observed CRC-TANKs, treatment pimozide, STAT5 inhibitor, reduced capability form networks, inhibiting VEGF production without affecting levels TIMP1, TIMP2, MMP9, indicating is cytokine modulation but not molecules. Combination Stat5 or MMP inhibitors immunotherapy help repolarize anti- antimetastatic ones.—Bruno, A., Bassani, B., D'Urso, D. G., Pitaku, I., Cassinotti, E., Pelosi, Boni, L., Dominioni, Noonan, M., Mortara, Albini, A. Angiogenin MMP9-TIMP2 axis up-regulated cancer. FASEB J. 32, 5365–5377 (2018). www.fasebj.org