TY - JOUR
T1 - The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis
AU - Goddard, Erica T.
AU - Hill, Ryan C.
AU - Nemkov, Travis
AU - D’Alessandro, Angelo
AU - Hansen, Kirk C.
AU - Maller, Ori
AU - Mongoue-Tchokote, Solange
AU - Mori, Motomi
AU - Partridge, Ann H.
AU - Borges, Virginia F.
AU - Schedin, Pepper
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/2
Y1 - 2017/2
N2 - Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a prometastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning BALB/c mice compared with nulliparous controls. Human relevance is suggested by a ∼3-fold increase in liver metastasis in patients with postpartum breast cancer (n = 564) and by liver-specific tropism (n = 117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer. SIGNIFICANCE: We find that patients with postpartum breast cancer are at elevated risk for liver metastasis. We identify a previously unrecognized biology, namely weaning-induced liver involution, that establishes a prometastatic microenvironment, and which may account in part for the poor prognosis of patients with postpartum breast cancer.
AB - Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a prometastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning BALB/c mice compared with nulliparous controls. Human relevance is suggested by a ∼3-fold increase in liver metastasis in patients with postpartum breast cancer (n = 564) and by liver-specific tropism (n = 117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer. SIGNIFICANCE: We find that patients with postpartum breast cancer are at elevated risk for liver metastasis. We identify a previously unrecognized biology, namely weaning-induced liver involution, that establishes a prometastatic microenvironment, and which may account in part for the poor prognosis of patients with postpartum breast cancer.
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U2 - 10.1158/2159-8290.CD-16-0822
DO - 10.1158/2159-8290.CD-16-0822
M3 - Article
C2 - 27974414
AN - SCOPUS:85011914837
SN - 2159-8274
VL - 7
SP - 177
EP - 187
JO - Cancer discovery
JF - Cancer discovery
IS - 2
ER -