Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 1065K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sedwick, C. Search for Related Content PubMed Articles by Sedwick, C. Social Bookmarking                            What's this?

Tumors' accomplices in invasion

Breast cancer cells (green) are more likely to metastasize to the lung if MSCs are around (right) to enhance their invasive ability. KARNOUB/MACMILLAN

Tumors that escape from their original site are associated with a poor prognosis for cancer patients. New research by Antoine Karnoub, Robert Weinberg (Whitehead Institute, Cambridge, MA), and colleagues suggests that the ability to escape may be acquired through the tumor's interactions with normal tissues.

A growing tumor is considered by its surrounding normal tissue to be a bit like a wound. As also occurs during the wound response, tumors recruit mesenchymal stem cells (MSCs)—which are meant to help with repair—from the bone marrow. Karnoub et al. hypothesized that these MSCs, rather than being helpful, may instead advance disease. To investigate this idea, they injected human breast cancer cells, either alone or along with human MSCs, into mice and then looked for metastases in the animals' lungs.

When MSCs were mixed with tumors, several cancer cell lines were more metastatic. This behavior was reversible; MSC-induced metastases purified from one animal and then injected without MSCs into new animals were no more metastatic than the original primary tumors. MSCs thus seem to teach cancer cells tricks that are not intrinsic to the cancer itself.

Some of these tricks might be learned from MSC-derived chemokines. The MSCs provided two lines of breast cancer cells with the chemokine CCL5, which caused the tumor cells to become more motile and invasive. MSCs had to contact cancer cells to make CCL5, but it is not known what interactions are important. And not every cancer line stimulated CCL5 production. "I liken it to a key-and-lock situation," says Karnoub. "The cancer has the key, but what lock it fits to release CCL5 from MSCs is a mystery."

Karnoub is also interested in how cancer cells cause long-term changes in MSC behavior. "The MSCs remembered having been in contact with tumor cells; even three days or more after their initial exposure, they were still making CCL5. There's a two-way communication going on there."

Reference:

Karnoub, A., et al. 2007. Nature. 449:557–565.[CrossRef][Medline]

Caitlin Sedwick

csedwick{at}gmail.com

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 1065K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sedwick, C. Search for Related Content PubMed Articles by Sedwick, C. Social Bookmarking                            What's this?