Event Title

Effect of PMN Presence on Cancer Vascularization in Colorectal Tumors of Mice

Session Number

Project ID: MEDH 09

Advisor(s)

Dr. Ronen Sumagin; Feinberg School of Medicine, Northwestern University

Dr. Triet Bui, Feinberg School of Medicine, Northwestern University

Discipline

Medical and Health Sciences

Start Date

20-4-2022 11:55 AM

End Date

20-4-2022 12:20 PM

Abstract

Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease (IBD), where deregulated immune responses promote exacerbated inflammation and formation of ulcers in the large intestine. IBD is also one of the high-risk factors for the development of colorectal cancer (CRC). Robust neutrophil infiltration is an important feature of both UC and CRC and in both cases, disease severity is clinically correlated with elevated neutrophil numbers in the tissue. Using a preclinical mouse model of CRC (AOM/DSS) and cell sequencing analyses, the Sumagin Lab found that tumor infiltrating neutrophils promote tumor vascularization by providing metalloproteinase-14 and Osteopontin. To confirm these findings at a protein level, tumor sections from early and advanced murine colon tumors induced by AOM/DSS treatment with and without prior elimination of tumor neutrophils were stained using immunohistochemistry for MMP-14, Spp1 and VEGFa, a known angiogenic factor. While VEGFa upregulation was neutrophil-independent, detailed image analyses revealed neutrophil-dependent induction of OPN expression in the tumor stroma and MMP14 in the tumor center specifically in advance tumors, consistent with the role of these factors in tumor vascularization and the rtole of neutrophils in CRC progression.

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Apr 20th, 11:55 AM Apr 20th, 12:20 PM

Effect of PMN Presence on Cancer Vascularization in Colorectal Tumors of Mice

Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease (IBD), where deregulated immune responses promote exacerbated inflammation and formation of ulcers in the large intestine. IBD is also one of the high-risk factors for the development of colorectal cancer (CRC). Robust neutrophil infiltration is an important feature of both UC and CRC and in both cases, disease severity is clinically correlated with elevated neutrophil numbers in the tissue. Using a preclinical mouse model of CRC (AOM/DSS) and cell sequencing analyses, the Sumagin Lab found that tumor infiltrating neutrophils promote tumor vascularization by providing metalloproteinase-14 and Osteopontin. To confirm these findings at a protein level, tumor sections from early and advanced murine colon tumors induced by AOM/DSS treatment with and without prior elimination of tumor neutrophils were stained using immunohistochemistry for MMP-14, Spp1 and VEGFa, a known angiogenic factor. While VEGFa upregulation was neutrophil-independent, detailed image analyses revealed neutrophil-dependent induction of OPN expression in the tumor stroma and MMP14 in the tumor center specifically in advance tumors, consistent with the role of these factors in tumor vascularization and the rtole of neutrophils in CRC progression.