Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

Song Li; Jie Zhou; Hongying Wu; Qianying Lu; Yanhong Tai; Qiang Liu; Chenguang Wang

doi:10.1080/15384101.2018.1511510

Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

Cell Cycle. 2018;17(16):2027-2040. doi: 10.1080/15384101.2018.1511510. Epub 2018 Sep 18.

Authors

Song Li¹, Jie Zhou², Hongying Wu¹, Qianying Lu¹, Yanhong Tai³, Qiang Liu¹, Chenguang Wang⁴

Affiliations

¹ a Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine , Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin , China.
² b Department of Endocrinology and Metabolism, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
³ c Department of Pathology , 307 Hospital of Chinese PLA , Beijing , China.
⁴ d Departments of Cancer Biology, Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center , Thomas Jefferson University , Philadelphia , PA , USA.

Abstract

The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.

Keywords: Breast cancer; ErbB2/Her2; cancer stem cell; clone evolution; epithelial-mesenchymal transition (EMT); heterogeneity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast / pathology*
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Movement / radiation effects
Cell Polarity / radiation effects
Cell Proliferation / radiation effects
Cell Transformation, Neoplastic / pathology*
Cell Transformation, Neoplastic / radiation effects
Coculture Techniques
Cytokines / metabolism
Epithelial Cells / pathology*
Epithelial Cells / radiation effects
Epithelial-Mesenchymal Transition / radiation effects
Female
Gamma Rays
Humans
Models, Biological
Receptor, ErbB-2 / metabolism

Substances

Cytokines
Receptor, ErbB-2

Grants and funding

This study was supported by the National Natural Science Foundation of China [31670859, 81572744]; CAMS Innovation Fund for Medical Science [2017-I2M-1-016]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2016ZX310068, 2016ZX310198, 2016RC310019, 2016RC310017]; PUMC Youth Fund and the Fundamental Research Funds for the Central Universities [3332016100,10023201601602]; Research Funds for the Innovation Team of IRM-CAMS [1650] (Q. L.). Work conducted at the Institute of Radiation Medicine was supported by the startup grant from the Chinese Academy of Medical Sciences (C.W.). This project is funded in part by the National Natural Science Foundation of China [81102006 (Y.T.)] and the Shandong Natural Science Foundation [Z2008C13].