Molecular Medicine Israel

Cancer Cells Fuse with Immune Cells in Human Patients

The hybrid cells promote tumor heterogeneity and possible metastasis, a new study in mice and humans shows.

More than a century ago, Otto Aichel, a German pathologist, made the peculiar observation of cancer cells with characteristics of different cell types, including white blood cells. The data led him to propose that the fusion between cancer cells and white blood cells could impose advantages to the tumor, allowing it to spread more readily in the body. But since then, evidence for the formation of these cancer cell–immune cell hybrids has been difficult to come by.

Now, Aichel’s theory just got a lot more support. In a study published yesterday (September 12) in Science Advances, researchers at the Oregon Health & Science University (OSHU) and their colleagues describe the presence of such hybrids in mouse models of cancer and in the peripheral blood of patients with solid tumors.

In the human cancer patients, the presence of these circulating hybrid cancer cells correlated with more advanced disease and poorer survival compared with patients who did not have detectable hybrids in their blood.

“This is an excellent study with a solid study design and appropriate controls, particularly as cell fusion is a notoriously difficult cellular process to study,” Brenda Ogle, who studies cell-cell fusion at the University of Minnesota’s Stem Cell Institute and who was not involved in the work, writes in an email to The Scientist. “The authors’ results expand on prior work [in mice] to the clinic and make a compelling case for tracking circulating hybrid cells as a means to predict stage and survival outcomes in cancer patients.”
OSHU’s Melissa Wong and her colleagues had previously demonstrated that culturing mouse colon cancer cells together with macrophages can result in cell hybrids with chromosomes from each cell type. They also provided hints that this process occurs in vivo.

In the new work, the team first validated that co-culturing mouse colon or melanoma cancer cell lines with macrophages resulted in a population of spontaneously fused hybrid cells. The researchers identified hybrid cells by looking for the simultaneous presence of recipient and donor fluorescent markers and sex chromosomes from both cell types present in the hybrid cells. They also captured the fusion process using live imaging and showed that the hybrids went on to divide.

The hybrid cells had a greater ability to migrate and invade in vitro compared to the unfused cancer cells, and when injected into mice, they more readily formed metastases compared to their nonhybrid cancer cell line counterparts. The researchers also observed spontaneous hybrid cells in mice injected with melanoma cells….

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