Understanding and Halting the Process of Metastasis

In preparation of a full-scale invasion of other organs within the body, malignant tumors secrete a chemical that selectively accumulates in distant target tissues, according to research published in the journal Cancer Cell. The chemical then attracts certain bone-marrow-derived cells that attack connective tissue in the organs, preparing a path for migrating cancer cells to follow.

According to cancer biologist at Stanford University, Amato Giaccia, metastasis is not a passive process. Cells don’t simply break off the primary tumor and lodge somewhere else. Instead, the cells actually secrete substances to precondition target tissue and make it more amenable to subsequent invasion.

When the researchers examined this chemical process, they found the elaborate dynamics of, and how to stop, the process of metastasis – the migration of cancer cells to faraway sites in the body to produce tumors that are even more malignant than the primary tumor. The team, which conducted the study on mice, is optimistic that the same results can be reproduced with humans.

It was previously known that certain types of cancer metastasize preferentially to specific parts of the body, and that certain cells that originate in the bone marrow congregate around that future colonization site, known as a pre-metastatic niche, and facilitates the malignant cells’ entry. Also previously known was that an enzyme called lysyl oxidase (LOX) somehow aids the process of metastasis.

In normal healthy tissue, LOX helps the growth of connective tissue. But tumors abnormally increase the production of LOX. And when LOX expression is suppressed in mice, cancer migration is halted as well. What the recent study discovered was the suppressing LOX in mice that had been injected with human breast cancer cells not only stopped the usually metastasis to the lungs but also prevented bone-marrow-derived CD11b cells from concentrating in the lungs and forming niches.

The researchers claimed that the CD11b cells secrete a protein that destroys the collagen in the connective tissue surrounding the lungs, allowing cancer cells a colonization point. Giaccia claims that we’ve never fully understood before how normal tissues were modified to allow metastases to target and successfully invade them.

We are now aware that LOX goes directly to the target tissue and attracts CD11b and other bone-derived cells to the pre-metastatic niche. If the mouse data is transferable to humans, and we have reasons to think it will be, we really believe we man have found an effective treatment method for human disease.

Further research published in Nature Cell Biology has found a cancer-fighting gene that converts organ cells that change into highly mobile stem cells back to their original stationary state. This newly discovered activity of the p53 gene offers a potential avenue of attack on breast  cancer cells thought to play a central role in progression and spread of the disease, according to researchers from The University of Texas MD Anderson Cancer Center.

Long known for monitoring DNA damage and causing defective cells to kill themselves, p53 also activates bits of RNA that inhibits two proteins, the researchers discovered. This prevents conversion of epithelial-differentiated cells, which line or cover an organ, into cells that resemble mesenchymal stem cells when stimulated by the TGF-B(beta) growth factors. Mesenchymal cells are mobile adult stem cells that have the potential to reproduce them cells and differentiate into a variety of cell types.

According to senior author, Mien-Chie Hung, blocking this conversion from epithelial cell to mesenchymal cell type is critical since that change plays an important role in cancer metastasis. Research has found that about 80 percent of all solid tumors start in the epithelial cells. However, 90 percent of cancer deaths are a result of metastasis. Stopping this process will be a central focus of future studies.


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