The European Society for Medical Oncology (ESMO) is slanted toward clinical medicine, and plenary sessions at the ESMO Virtual Congress 2020 featured phase III trials on approved drugs.

But there were smaller sessions devoted to basic science as well.

At one of those sessions, the Monday proffered paper session on basic science, several researchers shared new insights into metastasis.

Metastases are the cause of a large majority of cancer deaths, and treatment options against them remain far more limited than against primary tumors. By understanding their basic biology better, it may be possible to gain more of an upper hand against metastases, which currently mark the point when a cancer has become incurable.

Lone wolf or wolfpack?

To set up shop away from the primary tumor, metastatic cells first have to travel, and the dominant theory about how they do so could be described as the lone wolf theory.

But in some cases, cancer cells may travel more like a wolfpack.

Emmanuel Dornier, postdoctoral fellow at the Gustave Roussy Institute, described what he and his colleagues have termed TSIPs, for tumor spheres with inverted polarity. TSIPs, Dornier said, are "very efficient initiators of metastasis in colorectal cancer."

Dornier described the approach used in the lab of his mentor Fanny Jaulin as "translational cell biology."

"It is important to be as close to the patient as possible when you are studying invasion," he explained, and he and his colleagues have achieved this proximity by working cells they procure directly from surgeries and propagate as explants, organoids or patient-derived xenografts.

TSIPs were identified in Jaulin's lab, in work described in Nature Cell Biology in 2018, through profiling peritoneal effusions from colorectal cancer (CRC) patients with advanced metastatic disease.

When the team looked for cells that could seed metastases in the effusions, they found that they differed from the classic model of metastasis seeding cells in two ways.

First, Dornier recounted, "they were not actually single cells, but rather clusters of a few hundred cells" that "behaved like coordinated super-cells," enabling them to invade throughout the peritoneal space.

The cells also have inverted apical-basal polarity. Epithelial cells normally have an apical outside and a basal inside, but the TSIPs had basal markers on the outside. This reduced their adhesiveness to surfaces.

At the ESMO meeting, Dornier described new insights into how TSIPs migrate. His team demonstrated that the cells were propelled by a mechanism he called amoeboid migration, which depended on the contractility of the "molecular motor" proteins actin and myosin, which are best known for their role in muscle contraction.

"Collective amoeboid migration relies on the contractility of actin and myosin, and thus occurs in non-adhesive environments like the lumen of blood and lymphatic vessels," he explained. And "these are interfaces that cancers are going to find when they are doing their metastatic migration."

The findings have therapeutic implications; in their abstract, the researchers conclude their work "suggests that therapies targeting adhesive properties of cancer cells might be unsuccessful and unravels a new therapeutic avenue to limit the metastatic spread of CRCs." (Dornier, E. et al. Eur Soc Med Oncol (ESMO) Congr (Sept 18-22, Madrid) 2020, Abst 10 ; Zajac, O. et al. Nat Cell Biol 2018, 20: 296).

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