Circulating cancer cells can also return to and grow in their tumor of origin, according to researchers at Memorial Sloan-Kettering Cancer Center. They call this process self-seeding and believe that it sheds light on clinical observations such as the relationship between the tumor size, prognosis, and local relapse following seemingly complete removal of a primary breast tumor.
“We know there is an association between large tumor size and poor prognosis,” points out study co-author Larry Norton, M.D., deputy physician-in-chief for breast cancer programs at Memorial Sloan-Kettering. “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 tumor growth and distant metastases by similar mechanisms.”
The research titled “Tumor self-seeding by circulating cancer cells” was published in the December 25 issue of Cell.
According to the study 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 factors that are responsible for executing these functions: cytokines IL-6 and IL-8, which attract the most aggressive segment of the circulating tumor cell population, and MMP1/collagenase-1 and the actin cytoskeleton component fascin-1, which mediate the infiltration of circulating tumor cells into a tumor.
They also showed that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors like the chemokine CXCL1.
The study also found 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. Thus there is an increased potential to metastasize to these organs. Additional experiments revealed that self-seeding can occur in cancer cells of various tumor types besides 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 tumor progression,” says the study's senior author, Joan Massagu, Ph.D., chair of the cancer biology and genetics program at Memorial Sloan-Kettering.