Invasive lung cancer cells have distinct roles

When cancer cells split off from a tumor to seed deadly metastases, they are thought to travel as clusters or packs, a phenomenon known as collective invasion. The members of an invasive pack are not all alike, scientists at Winship Cancer Institute of Emory University have learned.

Lung cancer cells making up an invasive pack have specialized roles as leaders and followers, which depend on each other for mobility and survival, the scientists report in Nature Communications.

The differences between leaders and followers — and their interdependence — could be keys for future treatments aimed at impairing or preventing cancer metastasis, says senior author Adam Marcus, PhD, associate professor of hematology and medical oncology at Winship Cancer Institute and Emory University School of Medicine. Dr. Marcus is also a faculty member in the BCDB and CB programs.

“We’re finding that leader and follower cells have a symbiotic relationship and depend on each for survival and invasion,” he says. “Because metastatic invasion is the deadliest aspect of cancer, our goal is to find agents that disrupt that symbiotic relationship.”

Marcus and former CB graduate student Jessica Konen, PhD began by observing how a mass of lung cancer cells behaves when embedded in a 3-D protein gel. The cells generally stick together, but occasionally, a few cells extend out of the mass like tentacles, with the leader cell at the tip.

To study what makes leader and follower cells different from each other, Marcus and Konen developed a technique for marking the cultured cells with a laser, thus changing them from fluorescent green to red, and then isolating red cells. They call this technique SaGA, for spatiotemporal genomic and cellular analysis.

A video explaining SaGA won first prize in a contest organized by the Association of American Medical Colleges in 2015. Co-authors include CB graduate student Emily Summerbell, senior research scientist Bhakti Dwivedi, PhD and Winship faculty members Wei Zhou, PhD, Lawrence Boise, PhD, Paula Vertino, PhD, Lee Cooper, PhD, Khalid Salaita, PhD and Jeanne Kowalski, PhD. Dr. Zhou is a faculty member in the CB and GMB programs, Dr. Boise is a faculty member in the BCDB, CB and IMP programs, Dr. Vertino is a faculty member in the CB and GMB programs, and Dr. Cooper is a faculty member in the CB program.

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