A cancer cell under flow sits tight with uniform actin (green) if it can't see its own chemical cues (bottom).

SWARTZ/ELSEVIER

Like the proverbial donkey that follows the carrot, tumor cells follow chemical attractants. Unlike the donkey, however, the tumor cells even make their own carrots, according to a report by Melody Swartz, Jacqueline Shields, Mark Fleury (École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland), and colleagues.

The group was interested in how tumor cells migrate to lymphatic vessels—the first step in malignancy for most carcinomas. Migrating tumor cells express receptors for attractants that lymphatics normally produce to lure immune cells. Shields et al. now show that tumor cells don't need to rely on lymphatics to make the attractants they follow; they can produce the chemicals themselves.

A tumor cell would make no progress, however, if its secreted attractants were all around it. The group therefore predicted that the flow of tissue fluids toward draining lymphatics concentrates the attractants downstream, ensuring that they always dangle alluringly in front of the tumor cell. Computer modeling of this flow-induced migration supported their prediction.

The authors then mimicked the fluid dynamics and 3D structure of tumor tissue in culture. They found that blocking the attractant receptors on tumor cells prevented the cells from moving in the direction of the flow and prevented the reorganization of actin filaments to the leading edge that is necessary for migration. The amount of attractants secreted by different tumor cells correlated with the strength of their self-mobilization and with their metastatic potential in vivo.

It's not yet clear how this new paradigm of autonomous signal–following activity will be applicable to cancer therapy, although the results suggest that blocking a tumor's secreted chemokines may help prevent its spread. Swartz also envisages one far-out surgical possibility: the replacement of a tumor with a kind of sponge to reverse the direction of flow in the tissue and chemoattractively mop-up remaining metastatic cells from the tumor's locality.

Reference:

Shields, J., et al.
2007
.
Cancer Cell.
11
:
526
–538.