CD66 and CD49f expressing cells are associated with distinct neoplastic phenotypes and progression in human cervical cancer

Background: In this study, building on our recent work identifying a subset of CD66+ve cells with distinctive tumourigenic properties in human cervical cancers, we examine patterns of expression and function of these cells; to generate insights into the process of metastasis. Methods: Our broad approach in this study has been to compare the expression and function of two subsets marked by CD66 and CD49f. We use a combination of histopathology, immunostaining and flow cytometry, functional analysis of an established cervical cancer cell line and a retrospective analysis of a cohort of cervical cancer. Results: We noted CD66 expression associated with clusters of cells which are spindle shaped, SMA+ve, podoplanin+ve, phalloidin high, fibronectin high, plakoglobin low, ki67-ve and CK10+ve at the migratory phase along with features of partial EMT. Further, TGF beta 1 a well known regulator of EMT, positively correlated with CD66 expression. The additional CD49f+ve subset at the leading invading front of migration was SMA-ve, phalloidin low, fibronectin low, plakoglobin high, Ki67+ve and CK14+ve. These data are consistent with a role for CD66 cells in metastatic invasion with a collective cell migration process co-opting the CD49f subset. Our retrospective analysis of a cohort is consistent with a role for CD66 in metastasis. However, the broad analysis of CD66, CD49f and TGF beta 1 expression with patterns of overall survival points to a possible protective effect particularly for local recurrences. Hence, future studies focussing on potential heterogeneity within the CD66 subset along with the possible role of isoforms and intra-cellular roles would be essential. (C) 2016 The Authors. Published by Elsevier Ltd.