Tumor self-seeding by circulating cancer cells.
Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.
Kim
Mi-Young
MY
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Oskarsson
Thordur
T
Acharyya
Swarnali
S
Nguyen
Don X
DX
Zhang
Xiang H-F
XH
Norton
Larry
L
Massagué
Joan
J
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics
D009363:Neoplasm Proteins