Aswathy Ammothumkandy1, Tessy Thomas Maliekal2, Mayil Vahanan Bose3, Thangarajan Rajkumar3, Sundersingh Shirley4, B Thejaswini5, Venkat G Giri5, Sudhir Krishna6. 1. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. 2. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India; Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India. 3. Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai, India. 4. Department of Oncopathology, Cancer Institute (WIA), Adyar, Chennai, India. 5. Department of Radiotherapy, Kidwai Memorial Institute of Oncology, Bangalore, India. 6. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India. Electronic address: skrishna@ncbs.res.in.
Abstract
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, TGFβ1 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 TGFβ1 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.
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, TGFβ1 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 TGFβ1 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.
Authors: Yanzhu Lin; Fanqing Meng; Zhiyuan Lu; Kai Chen; Yalan Tao; Yi Ouyang; Xinping Cao Journal: Cancer Manag Res Date: 2018-10-04 Impact factor: 3.989