Cancers, Vol. 15, Pages 4646: Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression

Cancers, Vol. 15, Pages 4646: Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression Cancers doi: 10.3390/cancers15184646 Authors: Mary E. Vail Rae H. Farnsworth Linda Hii Stacey Allen Sakshi Arora Robin L. Anderson Ross A. Dickins Akira Orimo Sunny Z. Wu Alexander Swarbrick Andrew M. Scott Peter W. Janes Tumour progression relies on interactions with untransformed cells in the tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), which promote blood supply, tumour progression, and immune evasion. Eph receptor tyrosine kinases are cell guidance receptors that are most active during development but re-emerge in cancer and are recognised drug targets. EphA3 is overexpressed in a wide range of tumour types, and we previously found expression particularly in stromal and vascular tissues of the TME. To investigate its role in the TME, we generated transgenic mice with inducible shRNA-mediated knockdown of EphA3 expression. EphA3 knockdown was confirmed in aortic mesenchymal stem cells (MSCs), which displayed reduced angiogenic capacity. In mice with syngeneic lung tumours, EphA3 knockdown reduced vasculature and CAF/MSC-like cells in tumours, and inhibited tumour growth, which was confirmed also in a melanoma model. Single cell RNA sequencing analysis of multiple human tumour types confirmed EphA3 expression in CAFs, including in breast cancer, where EphA3 was particularly prominent in ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research