Modeling Tumor Metastasis In Vivo

TOPICAL COLLECTIONS

Guest Editors

Eason Hildreth

University of Alabama-Birmingham

Dr. Hildreth obtained his BS in Biology from East Carolina University and his DVM from North Carolina State University. He then completed a small animal rotating internship at the University of Florida and a small animal surgical residency at Ohio State University. During his residency, he completed a concurrent MS degree evaluating the use of PTHrP as an in vitro bone-forming agent. After his residency, he stayed at Ohio State to complete a PhD focused on the role of PTHrP in skeletal development and the use of PTHrP as a bone-forming agent. During his PhD, he developed an intense interest in the advanced imaging of bone using microCT, particularly in response to bone-forming therapies or genetic modification. This resulted in collaborations with multiple bone biology and cancer research laboratories. Upon completing his PhD in 2014 he was hired as an associate faculty member within the OSU-CVM as an Instructor of Small Animal Surgical Practice. In this role, he taught bone biology, general surgery, and orthopedics in the veterinary curriculum. Starting in 2015, he also joined the laboratory of Dr. Michael C. Ostrowski in the Comprehensive Cancer Center as a Post-Doctoral Fellow. His focus was investigating 1) the role of macrophages and osteoclasts in breast cancer bone metastasis and 2) transcription factors and microRNAs regulating osteoblast and osteoclast formation. In May 2017 he continuing his work with Dr. Ostrowski at the Medical University of South Carolina's Hollings Cancer Center. In October 2018 he was promoted to Research Assistant Professor after receiving a NIH K01 Award. In July 2019 he started a tenure track Assistant Professor position at the University of Alabama-Birmingham (UAB) in the Department of Pathology’s Division of Molecular and Cellular Pathology and the O’Neal Comprehensive Cancer Center, where his work focuses on the role of macrophages and osteoclasts in breast cancer bone metastasis and primary bone tumors.

Gina Sizemore

Ohio State University

Dr. Gina Sizemore is an assistant professor in the Department of Radiation Oncology at The Ohio State University School of Medicine, and a member of the Cancer Biology Program at The OSU-James Comprehensive Cancer Center. Dr. Sizemore’s research program integrates in vitro cell line and in vivo mouse modeling of the breast metastatic tumor microenvironment (TME) to provide mechanistic insight into breast cancer progression. Dr. Sizemore earned her BA in Biology at Washington and Jefferson College in 2003 and then spent two years as a research assistant for Dr. Dennis Slamon at the University of California, Los Angeles. She then matriculated to Case Western Reserve University in 2005 where she earned her PhD in Pharmacology in 2012 under Dr. Ruth Keri. After serving as a postdoctoral scholar there for about a year, Dr. Sizemore moved to OSU to gain expertise in the TME in the lab of Dr. Michael Ostrowski. There, from 2013-17 she was both a Pelotonia and Department of Defense Breast Cancer Research Program postdoctoral fellow. Following receipt of a K22 Transition Career Development Award from the National Cancer Institute in 2017, she then transitioned to tenure-track faculty in the Department of Radiation Oncology. Dr. Sizemore has been awarded numerous awards and fellowships over her career, including a METAvivor Young Investigator Award and the Herbert and Maxine Block Lectureship Junior Faculty Award. She has also authored/co-authored articles in prestigious journals including Nature Communications, Genes and Development, Molecular Cancer Research, Oncogene and The Journal of Biological Chemistry.

Collection Overview

For many tumor types, virtually all patient mortality is attributable to metastasis to distant organs. Metastasis requires a cancer cell to: intravasate into the associated vasculature, travel through the host bloodstream, adhere to the vasculature at a distant site, and finally extravasate into and colonize a target organ. The tumor cell must not only leave its primary tumor and survive the harsh journey, negotiating multiple steps along the way but eventually thrive and proliferate at its new location. Here, the tumor cells create an established metastasis that results in end-organ modification, increasing patient morbidity. During this time tumor, cells face a barrage of innate anti-cancer forces including hypoxia, host immunity, and competition with other resident cells for nutrition and survival. Given the critical importance of host cell interactions during metastatic progression, in vivo models are essential to faithfully recapitulate this complex process for hypothesis testing and drug development. This collection will present several current approaches to model metastasis in vivo. These may include: (1) experimental metastases models such as tail vein injection to predominantly model lung metastases, (2) intracarotid injection to model brain metastases, (3) intrathecal injection to model central nervous system metastases, and (4) multiple additional models involving tumor cell deposition into recognized sites of metastasis (intraosseous, intrahepatic, and intracranial injection). Many of these techniques hinge on the use of solid tumor models, but we will also present models of metastasis from hematogenous or “liquid” tumors such as leukemia and multiple myeloma. While experimental metastases and direct injection models are important tools to study the late stages of metastasis, spontaneous metastasis models are specifically required to study the complete metastatic cascade. These models begin with the injection of cancer cells at their orthotopic site followed by delayed ablation/resection of the primary tumor. This allows for a period for metastasis development and mirrors what is observed clinically when patients develop metastasis after a period following the removal of their primary tumor. Together, the models described in this collection should be useful for all investigators of cancer metastasis.