The findings of the study, published in the December 25 issue of the journal Cell, suggest that self-seeding can enhance tumour growth through the release of signals that promote angiogenesis, invasion, and metastasis.
"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 tumour 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 tumour to attract its own circulating progeny and the ability of circulating tumour cells to re-infiltrate the tumour 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 tumour cells population, and FSCN1 and MMP1, which mediate the infiltration of circulating tumour cells into a tumour.
The findings also show that circulating breast cancer cells that are capable of self-seeding a breast tumour 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. Additional experiments revealed that self-seeding can occur in cancer cells of various tumour types in addition to breast cancer, including colon cancer and melanoma.
"These results provide us with opportunities to explore new targeted therapies that may interfere with the self-seeding process and perhaps slow or even prevent tumour progression," said the study's senior author, Joan Massagué, PhD, Chair of the Cancer Biology and Genetics Program at Memorial Sloan-Kettering and a Howard Hughes Medical Institute investigator.
The concept of self-seeding sheds light on clinical observations such as the relationship between the tumour size, prognosis, and local relapse following seemingly complete removal of a primary breast tumour. "We know there is an association between large tumour size and poor prognosis. This was always thought to reflect the ability of larger cancers to release more cells with metastatic potential. But this association may actually be caused by the ability of aggressive cancer cells to self-seed, promoting both local tumour growth and distant metastases by similar mechanisms," said study co-author Larry Norton, MD, Deputy Physician-in-Chief for Breast Cancer Programs at Memorial Sloan-Kettering.
