Placenta-conditioned extracellular matrix (ECM) activates breast cancer cell survival mechanisms: A key for future distant metastases

Oded Komemi, Gali Epstein Shochet, Meir Pomeranz, Ami Fishman, Metsada Pasmanik-Chor, Liat Drucker, Shelly Tartakover Matalon, Michael Lishner

Research output: Contribution to journalArticlepeer-review

Abstract

The extracellular matrix (ECM) affects cancer cell characteristics. Inability of normal epithelial cells to attach to the ECM induces apoptosis (anoikis). Cancer cells are often anoikis resistant, a prerequisite for their metastatic spread. Previously we demonstrated that the placenta manipulates its surrounding ECM in a way that prevents breast cancer cells (BCCL) attachment and induces their motility and aggregation. This fits with the fact that although breast cancer during pregnancy is often advanced, metastasis to the placenta is rarely observed. Placental intervillous space provides suitable conditions for cancer cell arrival. Yet, the outcome of the short communication between the placental ECM to the BCCL and its effect on BCCL malignant potential are unknown, and are the focus of our study. In the current study we analyzed the effect of placental ECM on BCCL survival pathways and drug resistance. Microarray analysis suggested activation of the NF-κB and stress response pathways. Indeed, the placenta-conditioned ECM induced autophagy in ERα + BCCL, inactivated the NF-κB inhibitor (IκB) and increased integrin α5 in the BCCL. The autophagy mediated MCF-7 and T47D migration and the placental ECM-BCCL interactions reduced the BCCL sensitivity to Taxol. We also demonstrated by using siRNA that integrin α5 was responsible for the MCF-7 autophagy and suggest this molecule as a suitable target for therapy.

Original languageEnglish
Pages (from-to)1633-1644
Number of pages12
JournalInternational Journal of Cancer
Volume144
Issue number7
DOIs
StatePublished - 1 Apr 2019

Keywords

  • ECM
  • breast cancer
  • metastasis
  • placenta
  • survival pathways

Fingerprint

Dive into the research topics of 'Placenta-conditioned extracellular matrix (ECM) activates breast cancer cell survival mechanisms: A key for future distant metastases'. Together they form a unique fingerprint.

Cite this