How ‘jail-breaker’ cancer cells escape

PRINCETON (US) — Cancer cells that can break out of a tumor and invade other organs are more aggressive than nonmalignant cells and are nimble enough to maneuver their way into small spaces.

A systematic comparison of metastatic breast cancer cells to healthy breast cells revealed dramatic differences between the two cell lines in their mechanics, migration, oxygen response, protein production, and ability to stick to surfaces.

The new study details how cells make the transition from nonmalignant to metastatic, a process that is not well understood.

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Published in the journal Scientific Reports, the findings could someday help detect cancerous cells earlier and prevent or treat metastatic cancer, which is responsible for 90 percent of all cancer deaths.

“By bringing together different types of experimental expertise to systematically compare metastatic and nonmetastatic cells, we have advanced our knowledge of how metastasis occurs,” says Robert Austin, professor of physics at Princeton University.

Researchers determined that in spite of moving more slowly than nonmalignant cells, metastatic cells move farther and in a straighter line. The investigators studied the cells’ behavior in tiny cell-sized chambers and channels etched out of silicon and designed to mimic the natural environment of the body’s interior.

“The mobility of these metastatic cells is an essential feature of their ability to break through the tough membrane (the extracellular matrix) that the body uses to wall off the tumor from the rest of the body. These cells are essentially jail-breakers,” Austin says.

The tiny silicon chambers were built using microfabrication technology—typically used to create small technologies such as integrated circuits and solar cells.

Vigorous rebound

The study also found that metastatic cells recover more rapidly from the stress of a low-oxygen environment than nonmetastatic cells, which is consistent with previous studies. Although the low-oxygen environment did kill many of the metastatic cells, the survivors rebounded vigorously, underscoring the likely role of individual cells in the spread of cancer.

The study also looked at total protein production and detected proteins in the metastatic cells that are consistent with the physical properties such as mobility that malignant cells need to invade the extracellular matrix.

For the nationwide project, nearly 100 investigators from 20 institutions and laboratories conducted their experiments using the same two cell lines, reagents, and protocols to assure that results could be compared. The experimental methods ranged from physical measurements of how the cells push on surrounding cells to measurements of gene and protein expression.

For example, a technique known as atomic force microscopy indicated that metastatic cells are softer than nonmalignant cells whereas a different technique, traction force microscopy, suggested that metastatic cells exert more force on their surroundings.

Together these two findings may indicate that metastatic cells can exert force to stick to, migrate on and remodel the tough extracellular matrix that surrounds the tumor, while remaining flexible enough to squeeze through small spaces in that membrane.

The research was conducted by a network of 12 federally funded Physical Sciences-Oncology Centers (PS-OC) sponsored by the National Cancer Institute. PS-OC is a collaboration of researchers in the physical and biological sciences seeking a better understanding of the physical and chemical forces that shape the emergence and behavior of cancer.

Researchers from Johns Hopkins University School of Medicine, the Salk Institute for Biological Studies, the University of California, Santa Cruz, and the University of California, San Francisco contributed to the study.

Source: Princeton University