Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance

Fei Su, Songyeon Ahn, Achinto Saha, John DiGiovanni, Mikhail G. Kolonin

Research output: Contribution to journalArticle

Abstract

Fat tissue, overgrowing in obesity, promotes the progression of various carcinomas. Clinical and animal model studies indicate that adipose stromal cells (ASC), the progenitors of adipocytes, are recruited by tumors and promote tumor growth as tumor stromal cells. Here, we investigated the role of ASC in cancer chemoresistance and invasiveness, the attributes of tumor aggressiveness. By using human cell co-culture models, we demonstrate that ASC induce epithelial-mesenchymal transition (EMT) in prostate cancer cells. Our results for the first time demonstrate that ASC interaction renders cancer cells more migratory and resistant to docetaxel, cabazitaxel, and cisplatin chemotherapy. To confirm these findings in vivo, we compared cancer aggressiveness in lean and obese mice grafted with prostate tumors. We show that obesity promotes EMT in cancer cells and tumor invasion into the surrounding fat tissue. A hunter-killer peptide D-CAN, previously developed for targeted ASC ablation, suppressed the obesity-associated EMT and cancer progression. Importantly, cisplatin combined with D-CAN was more effective than cisplatin alone in suppressing growth of mouse prostate cancer allografts and xenografts even in non-obese mice. Our data demonstrate that ASC promote tumor aggressiveness and identify them as a target of combination cancer therapy.

LanguageEnglish (US)
JournalOncogene
DOIs
StateAccepted/In press - Jan 1 2018

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Epithelial-Mesenchymal Transition
Stromal Cells
Prostatic Neoplasms
Neoplasms
Cisplatin
Obesity
docetaxel
Fats
Obese Mice
Growth
Coculture Techniques
Adipocytes
Heterografts
Cell Communication
Allografts
Prostate
Animal Models

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Adipose stromal cell targeting suppresses prostate cancer epithelial-mesenchymal transition and chemoresistance. / Su, Fei; Ahn, Songyeon; Saha, Achinto; DiGiovanni, John; Kolonin, Mikhail G.

In: Oncogene, 01.01.2018.

Research output: Contribution to journalArticle

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