The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis

Erica T. Goddard, Ryan C. Hill, Travis Nemkov, Angelo D’Alessandro, Kirk C. Hansen, Ori Maller, Solange Mongoue-Tchokote, Motomi (Tomi) Mori, Ann H. Partridge, Virginia F. Borges, Pepper Schedin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)177-187
Number of pages11
JournalCancer Discovery
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2017

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Weaning
Rodentia
Breast Neoplasms
Neoplasm Metastasis
Liver
Postpartum Period
Circulating Neoplastic Cells
Tenascin
Tropism
Myeloid Cells
Extracellular Matrix
Weight Loss
Hepatocytes
Collagen
Apoptosis

ASJC Scopus subject areas

  • Oncology

Cite this

Goddard, E. T., Hill, R. C., Nemkov, T., D’Alessandro, A., Hansen, K. C., Maller, O., ... Schedin, P. (2017). The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. Cancer Discovery, 7(2), 177-187. https://doi.org/10.1158/2159-8290.CD-16-0822

The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. / Goddard, Erica T.; Hill, Ryan C.; Nemkov, Travis; D’Alessandro, Angelo; Hansen, Kirk C.; Maller, Ori; Mongoue-Tchokote, Solange; Mori, Motomi (Tomi); Partridge, Ann H.; Borges, Virginia F.; Schedin, Pepper.

In: Cancer Discovery, Vol. 7, No. 2, 01.02.2017, p. 177-187.

Research output: Contribution to journalArticle

Goddard, ET, Hill, RC, Nemkov, T, D’Alessandro, A, Hansen, KC, Maller, O, Mongoue-Tchokote, S, Mori, MT, Partridge, AH, Borges, VF & Schedin, P 2017, 'The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis', Cancer Discovery, vol. 7, no. 2, pp. 177-187. https://doi.org/10.1158/2159-8290.CD-16-0822
Goddard ET, Hill RC, Nemkov T, D’Alessandro A, Hansen KC, Maller O et al. The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. Cancer Discovery. 2017 Feb 1;7(2):177-187. https://doi.org/10.1158/2159-8290.CD-16-0822
Goddard, Erica T. ; Hill, Ryan C. ; Nemkov, Travis ; D’Alessandro, Angelo ; Hansen, Kirk C. ; Maller, Ori ; Mongoue-Tchokote, Solange ; Mori, Motomi (Tomi) ; Partridge, Ann H. ; Borges, Virginia F. ; Schedin, Pepper. / The rodent liver undergoes weaning-induced involution and supports breast cancer metastasis. In: Cancer Discovery. 2017 ; Vol. 7, No. 2. pp. 177-187.
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