Work

A Novel in vivo Rat Mesentery Model for Studying Tumor Spheroid-Induced Microvascular Remodeling

Year: 2024

Type: article

Abstract: INTRODUCTION: The tumor microenvironment is comprised of neoplastic cells and a variety of host cell types. Investigation of cell dynamics within this environment has motivated in vitro and ex vivo biomimetic model development. Our laboratory recently introduced the tumor spheroid-rat mesentery culture model to investigate cancer-induced lymphatic/blood vessel remodeling. To validate the physiological relevance of this model, the objective of this study was to determine the effect of tumor spheroids on microvascular remodeling after transplantation onto rat mesenteric tissues in vivo. METHODS: Spheroids derived from H1299 lung cancer cells were seeded onto rat mesenteric tissues during a survival surgical procedure. Tissues were harvested 3-5 days post-seeding and stained with PECAM and LYVE-1 to identify blood and lymphatic vessels, respectively. RESULTS: At all timepoints, cancer cells remained adhered to the tissue. Tissues seeded with tumor spheroids were shown to have increased vascular density, capillary sprouting, and tortuosity compared to sham tissues exposed to sterile saline only. Tumor spheroids also induced the formation of lymphatic/blood vessel connections and LYVE-1-negative protrusions emerging from lymphatic vessels. CONCLUSION: Overall, this study underscores the use of in vivo modeling to aid in the discovery of novel vascular growth dynamics and offers new methodologies for studying tumor-induced remodeling. INTRODUCTION: The tumor microenvironment is comprised of neoplastic cells and a variety of host cell types. Investigation of cell dynamics within this environment has motivated in vitro and ex vivo biomimetic model development. Our laboratory recently introduced the tumor spheroid-rat mesentery culture model to investigate cancer-induced lymphatic/blood vessel remodeling. To validate the physiological relevance of this model, the objective of this study was to determine the effect of tumor spheroids on microvascular remodeling after transplantation onto rat mesenteric tissues in vivo. METHODS: Spheroids derived from H1299 lung cancer cells were seeded onto rat mesenteric tissues during a survival surgical procedure. Tissues were harvested 3-5 days post-seeding and stained with PECAM and LYVE-1 to identify blood and lymphatic vessels, respectively. RESULTS: At all timepoints, cancer cells remained adhered to the tissue. Tissues seeded with tumor spheroids were shown to have increased vascular density, capillary sprouting, and tortuosity compared to sham tissues exposed to sterile saline only. Tumor spheroids also induced the formation of lymphatic/blood vessel connections and LYVE-1-negative protrusions emerging from lymphatic vessels. CONCLUSION: Overall, this study underscores the use of in vivo modeling to aid in the discovery of novel vascular growth dynamics and offers new methodologies for studying tumor-induced remodeling.

Source: Journal of Vascular Research

DOI: 10.1159/000543011

Authors: Arinola O. Lampejo, Luciana Fonseca Perez, Miriam M. Girgis, Blanka Sharma, Dietmar W. Siemann, Walter L. Murfee

Institutions: University of Florida, UF Health Cancer Center

Language: English

Topic: Lymphatic System and Diseases

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: American Heart Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute