Circulating tumor cells found to form clusters that cause breast cancer metastases

A new study by researchers from Northwestern Medicine reports that circulating tumor cells (CTCs) that exhibit the features of stem cells employ ICAM1, an adhesive protein, to enable the formation of CTC clusters.

Circulating tumor cells found to form clusters that cause breast cancer metastases
Huiping Liu, MD, PhD, associate professor of Pharmacology, was senior author of the study published in Nature Communications. Image Credit: Northwestern Medicine.

The study has been published in the Nature Communications journal.

The CTC clusters can move from primary tumors to other organs in the body and thus constitute a key source of metastases in breast cancer. Therefore, inhibition of tumor cell ICAM1 can block tumor cell seeding and suppress the progression of cancer, says Huiping Liu, MD, Ph.D., senior author of the study and associate professor of Pharmacology.

An antibody to neutralize the function of ICAM1 could reduce social networking of tumor cells during circulation and migration, and improve outcomes for patients with breast cancer.”

Huiping Liu, Associate Professor of Pharmacology, Northwestern Medicine

Liu is also a professor of Medicine in the Division of Hematology and Oncology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

In contrast to cancers presenting single CTCs, cancers that present with CTC clusters are related to decreased survival in breast cancer and are 20 to 100 times more efficient at developing metastases, or further tumors outside the breast. Liu notes that breast cancer metastases occur in 90% of breast cancer deaths. “When the disease starts to spread into distant organs, it is almost always incurable,” she added.

Multicellular CTC clusters form the seeds of these metastases. These clusters, including two or three cells, become powerful due to their numbers while moving to other organs in the body.

In this study, Liu and her colleagues used patient-derived cancer cells to investigate cluster formation. They identified that the cells need the protein ICAM1—not just for the initial clustering but also for traveling through blood vessel walls as they move along the bloodstream.

They present ICAM1 on the cell surface to recognize each other and ‘hold hands’. It also helps them penetrate the endothelial layer outside of blood vessels.”

Huiping Liu, Associate Professor of Pharmacology, Northwestern Medicine

Moreover, clustered cancer cells behave like stem cells and more effectively develop offspring that can finally form a tumor. The depletion of ICAM1 from CTCs brought down the migration, suppressed the formation of distant tumors, and hindered their ability to enter into and out of blood vessels.

In the future, researchers can use an antibody that attaches to ICAM1 and decreases its function in breast cancer patients with high levels of ICAM1 or CTC clusters, thereby slowing down metastases and potentially prolonging survival.

Using ICAM1 as a biomarker, I think these patients would be excellent targets for an antibody treatment. This could be especially valuable in immunocompromised patients.”

Huiping Liu, Associate Professor of Pharmacology, Northwestern Medicine

Source:
Journal reference:

Taftaf, R., et al. (2021) ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer. Nature Communications. doi.org/10.1038/s41467-021-25189-z.

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