"There has been an undeniable link between tumor size and growth and metastatic risk, but the molecules and mechanisms underlying this link have remained unresolved," said Massagué. "The hypothesis we wanted to test was that these signature genes play a role in both primary tumor growth and metastasis to the lung."
After analyzing 738 human breast cancer tumors, the researchers concluded that those in which the LMS genes were abnormally active were, indeed, more likely to develop lung metastases. They also found that the activity of these LMS genes gave cancer cells a growth advantage by allowing tumors to develop a rich network of blood vessels to deliver oxygen and nutrients, said Massagué.
Although large tumors are more likely to metastasize, Massagué said his group’s findings indicated that the activity of the LMS genes was also critical to the metastasis process. "As the tumors grow and become enriched with LMS-positive cells, because the genes give them an advantage, they reach a point where the tumor becomes richly vascularized," said Massagué. "Then, they can massively execute the advantage the LMS genes provide them to metastasize to the lung."
Massagué said he and his colleagues will explore in more detail the function of other LMS genes, in addition to the four reported in the Nature paper. They plan to investigate whether shutting down other LMS genes will affect metastasis of breast cancer to the lung, and whether the LMS genes influence breast cancer metastasis to other sites, such as the bone and brain. Finally, they will explore whether the LMS genes play a corresponding role in metastasis of other cancers -- such as sarcoma, melanoma and colon cancer -- to the lung, said Massagué.
Source:Howard Hughes Medical Institute