Cancer progression is commonly thought of as a process involving the growth of a primary tumor followed by metastasis, in which cancer cells leave the primary tumor and spread to distant organs. A new study by researchers at Memorial Sloan-Kettering Cancer Center shows that circulating tumor cells –- the cancer cells that break away from a primary tumor and disseminate to other areas of the body -– can also return to and grow in their tumor of origin, a newly-discovered process called "self-seeding."
The findings of the study, published in the December 25 issue of the journal Cell, suggest that self-seeding can enhance tumor growth through the release of signals that promote angiogenesis, invasion and metastasis. Angiogenesis is a normal and vital process in human growth and development, as well as in wound healing. However, it is also one fundamental step in the transition of tumors from a dormant state to a malignant one.
"Our work not only provides evidence for the self-seeding phenomenon and reveals the mechanism of this process, but it also shows the possible role of self-seeding in tumor progression," said the study's first author, Mi-Young Kim, PhD, Research Fellow in the Cancer Biology and Genetics Program at Memorial Sloan-Kettering.
According to the research, which was conducted in mice, self-seeding involves two distinct functions: the ability of a tumor to attract its own circulating progeny and the ability of circulating tumor cells to re-infiltrate the tumor in response to this attraction. The investigators identified four genes that are responsible for executing these functions: IL-6 and IL-8, which attract the most aggressive segment of the circulating tumor cells population, and FSCN1 and MMP1, which mediate the infiltration of circulating tumor cells into a tumor.
The findings also show that circulating breast cancer cells that are capable of self-seeding a breast tumor have a similar gene expression pattern to breast cancer cells that are capable of spreading to the lungs, bones and brain, and therefore have an increased potential to metastasize to these organs.