Scientists identify 'critical' gene for development and spread of lung cancer

Scientists from the Mayo Clinic have identified a single gene that appears to be a major driving force in the development and spread of the most common form of lung cancer.  The study also suggested the gene may play a role in a number of other different types of cancer.

Matrix metalloproteinase-10 (MMP-10) is a growth factor gene used by cancer stem-like cells to keep themselves healthy, as well as migrate into the bloodstream or lymph nodes.  Thanks in part to MMP-10, these stem cells are highly resistant to cancer treatments.

“This family of [MMP] genes have been implicated for a long time in the process of metastasis – the ability of tumors to migrate out of the primary site and survive and move to a distal site,” Dr. Alan P. Fields, the Monica Flynn Jacoby Professor of Cancer Research at Mayo Clinic in Florida, told

According to Fields, metastasis depends on the ability of MMP genes to degrade the stroma – or the environment surrounding the tumor.  The stroma normally provides structure for tissues and acts as a barrier against cancer cells.

However, it was a surprise to researchers when they found that MMP was not only involved in metastasis, but also in the earliest stages of tumor growth.

“In a mouse model of lung cancer, when we inhibited MMP, we found these animals were deficient in their ability to initiate tumors when we attempted to activate tumor formations,” Fields said.  “We expected the tumors would form, but not progress to the point of metastasizing.  But the tumors never started growing.”

The study suggested it was the overexpression of MMP-10 specifically that drives the cancer stem cells.  In normal tissues, the amount of MMP-10 is very low, but in cancerous tissues it is expressed much more highly.  Besides lung cancer, MMP-10 is also suspected to play a role in colorectal, breast, prostate, ovarian and kidney cancers, as well as melanoma and renal cell carcinoma.

The finding suggests drugs or compounds that inhibit MMP-10 activity could be effective as anti-tumor agents – with the potential to prevent the spread of tumors or even cause them to regress.

Current cancer treatments, such as chemotherapy, target the cells that make up the bulk of a tumor.  But because the cancer-driving stem cells are left intact, the cancer can – and often does – return.

“Tumor stem cells are very resistant to these therapeutic agents, so they remain at the site of the tumor even as the tumor regresses and the patient goes it to remission,” Fields explained.  “Then what happens is you see a relapse or recurrence of the tumor due to these stem cells.”

“That’s the reason why we believe an MMP-10 inhibitor may be more effective, because it targets the tumor stem cells themselves,” he added.  “Even if you don’t target [the bulk of the tumor cells], they cannot survive long-term.  Eventually they will stop dividing and die, and the tumor will slowly regress and not come back because there’s no stem cell population that can bring it back.”

Prior treatments that have targeted MMP genes in clinical trials have not been tolerated well by patients – though Fields believes this may be because the drugs developed were not specific enough.

“The drugs developed were not highly specific for any MMP,” Fields said.  “MMPs are a family of genes that are related but serve different functions – and some are very important.  Selectively inhibiting MMP-10 could more effective as an anti-cancer agent with fewer toxicity issues.”

The study was published Tuesday in the journal PLoS ONE.