Abstract 1229: Neoadjuvant therapy alters collagen architecture of pancreatic cancer

Abstract

Abstract Treatment of pancreatic cancer remains clinically challenging and requires the novel therapeutic interventions to improve patient outcome. Neoadjuvant therapy i.e. preoperative treatments comprising chemotherapeutic agents with/without radiation offers down-staging and improvement of surgical resectability. Here, we report that neoadjuvant therapy alters collagen architecture of pancreatic cancer. Transcriptomic profiles of type 1 to type 28 collagens depicted changes of collagen composition due to neoadjuvant therapy. Immunohistochemically, the expressed area of collagen type 1, 3, 4, and 5 were significantly reduced post treatment. The bioinformatic approaches provided a comprehensive insight into treatment-induced matrix remodeling, which showed that Ephrin-A signaling and Ephrin-A5 appeared as a highly possible pathway and a crucial ligand. Ephrin-A5 co-localized with alpha-SMA(+) cancer-associated fibroblasts, whereby Ephrin-A5 have been implicated to synthesize collagens. The Ephrin-A5 positive cells significantly reduced after neoadjuvant therapy, also inversely correlated with tumor shrinkage rate. Using primary culture cells of cancer-associated fibroblasts, experimental exposure of radiation and chemotherapeutic agents suppressed the proliferation of cancer-associated fibroblasts, collagen synthesis and Ephrin-A5 expression. Thus, our studies demonstrate that neoadjuvant therapy down-regulates Ephrin-A5 expression, leading to a change of extracellular matrix structure. It should be a clinical concern of surgical handling when following resection. Note: This abstract was not presented at the meeting. Citation Format: Kosei Nakajima, Yoshinori Ino, Sotoshi Nara, Toshimitsu Iwasaki, Nobuyoshi Hiraoka. Neoadjuvant therapy alters collagen architecture of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1229.