Disseminated tumor cells (DTCs)—cancer cells that leave the primary tumor, survive in the bloodstream, and grow within a distant organ—are responsible for metastatic cancers, which cause approximately 90% of cancer deaths. The primary tumor’s microenvironment is thought to “educate” DTCs to successfully seed into metastatic tumors, but how that happens is unclear.
In a study published online on February 2 in Nature Communications, Albert Einstein College of Medicine scientists report that macrophages—immune cells previously implicated in metastasis—play a key role in programming cancer cells within primary tumors to successfully metastasize. After transplanting mouse and human breast tumors into mice, the researchers used high-resolution intravital imaging to follow DTCs in real time as they enter blood vessels at tumor microenvironment of metastasis (TMEM) doorways, travel through the bloodstream, and then, finally, escape from the blood vessels into the animals’ lung tissue.
This study, along with findings from the group’s 2021 Nature Communications study, shows that a subset of macrophages surrounding TMEM doorways within the primary tumor programs DTCs to become metastatic by equipping them with a “triple threat phenotype”: pro-dissemination (capable of entering and exiting blood vessels), pro-dormancy (capable of resisting chemotherapy, which targets dividing cells), and pro-stem (capable of initiating tumors). These studies also identify a new set of biomarkers that, if detected in the primary tumor, may indicate whether the cancer will spread and prove resistant to chemotherapy.
The senior author is David Entenberg, Ph.D., assistant professor of pathology and co-director of the Gruss-Lipper Biophotonics Center at Einstein. The lead author is Lucia Borriello, Ph.D., a postdoctoral fellow at Einstein. Other Einstein authors are John Condeelis, Ph.D., the Judith & Burton P. Resnick Chair in Translational Research; Julio A. Aguirre-Ghiso, Ph.D., endowed professor of cell biology, of medicine, director of the Institute for Cancer Dormancy and Tumor Microenvironment, and co-director of the Gruss-Lipper Biophotonics Center and Maja H. Oktay, M.D., Ph.D., professor of pathology and director of the New York Pathology Oncology Group.
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Posted on: Wednesday, February 02, 2022