Relevance of circulating hybrid cells as a non-invasive biomarker for myriad solid tumors

Matthew S. Dietz, Thomas L. Sutton, Brett S. Walker, Charles E. Gast, Luai Zarour, Sidharth K. Sengupta, John R. Swain, Jennifer Eng, Michael Parappilly, Kristen Limbach, Ariana Sattler, Erik Burlingame, Yuki Chin, Austin Gower, Jose L.Montoya Mira, Ajay Sapre, Yu Jui Chiu, Daniel R. Clayburgh, Su Ellen J. Pommier, Jeremy P. CetnarJared M. Fischer, Jerry J. Jaboin, Rodney F. Pommier, Brett C. Sheppard, V. Liana Tsikitis, Alison H. Skalet, Skye C. Mayo, Charles D. Lopez, Joe W. Gray, Gordon B. Mills, Zahi Mitri, Young Hwan Chang, Koei Chin, Melissa H. Wong

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the potential to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.

Original languageEnglish (US)
Article number13630
JournalScientific Reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

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