Relevance of circulating hybrid cells as a non-invasive biomarker for myriad solid tumors
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2021
- Source ID
- 10.1038/s41598-021-93053-7
Entities
People
- Ajay Sapre
- Alison H. Skalet
- Ariana Sattler
- Austin Gower
- Brett C. Sheppard
- Brett S. Walker
- Charles D. Lopez
- Charles E. Gast
- Daniel R. Clayburgh
- Erik Burlingame
- Gordon B. Mills
- Jared M. Fischer
- Jennifer Eng
- Jeremy P. Cetnar
- Jerry J. Jaboin
- Joe W. Gray
- John R. Swain
- Jose L. Montoya Mira
- Koei Chin
- Kristen Limbach
- Luai Zarour
- Matthew S. Dietz
- Melissa Wong
- Michael Parappilly
- Rodney F. Pommier
- Sidharth K. Sengupta
- Skye C. Mayo
- Suellen J. Pommier
- Thomas L. Sutton
- V. Liana Tsikitis
- Young Hwan Chang
- Yu-jui Chiu
- Yuki Chin
- Zahi Mitri
Organizations
- American Association for Cancer Research
- Collins Medical Trust
- Medical Research Foundation
- Melanoma Research Foundation
- National Cancer Institute
- National Center for Advancing Translational Sciences
- National Center for Research Resources
- National Institutes of Health
- United States Department of Defense