Cancer Throws Another Curveball

Metastasis of solid cancer tumors is a crucial step in progression and generally portends poor patient outcome. Circulating tumor cells (CTCs) in blood have been implicated as the mechanism for spreading tumors from the primary site. Most methods reported for isolating CTCs focus on CTCs at the single-cell level. However, a report in Scientific American1 by Viviane Callier indicates that 95% of secondary colonies occur from circulating clumps of tumor cells.

Callier cites research from the lab of Prof. Andrew Ewald of Johns Hopkins University.2 The experiment involved removing tumor cells from mice and engineering them to fluoresce red and green. The cells were injected into mice mammary glands to mimic metastasis. The hypothesis was that if CTCs at the single-cell level were effective in colonizing a new tissue, the resulting tumor would be one color. Two or more colors co-located in the new tumor would be an indication that many cells were involved at the metastasis site, and microscopic examination confirmed this in 95% of the secondary tumors.

A subsequent experiment showed that single cancerous cells in a Petri dish usually died, but when multiple cells aggregated together, they survived and formed more colonies. The relative growth rate was more than 100 times for the aggregates. Further, keratin 14 (K14) expressing tumor cells proved to be the most invasive.

The implication is clear—circulating tumor cells are out, replaced by circulating tumor aggregates. Analytical methods for counting single-cell CTCs may focus on cells that have little chance of surviving and colonizing. Methods that focus on circulating clusters of CTCs, such as magnetic beads or NanoVelcro (developed at UCLA’s California NanoSystems Institute), should be further investigated. NanoVelcro and magnetic beads support affinity ligands that target markers on the surface of cancer cells.

References

  1. http://www.scientificamerican.com/article/cancerous-coconspirators-tumor-cells-that-travel-together-spread-cancer/
  2. Cheung, K.J.; Padmanaban, V. et al. Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters. Proc. Natl. Acad. Sci. USA  2016 Feb 16, 113(7), E854-63; doi:10.1073/pnas.1508541113.

Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected].

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