Cancer Care through Early Detection & Intervention: NFCR

Tumor Microenvironment

Tumor Microenvironment

What is Tumor Microenvironment?

The tumor microenvironment encompasses the complex cellular ecosystem surrounding a tumor that plays a critical role in supporting or restraining cancer progression. Understanding tumor-microenvironment interactions has emerged as a therapeutic frontier for developing more effective cancer treatments.

Key components of the tumor microenvironment include stromal cells, immune cells, vasculature, extracellular matrix, and secreted factors like cytokines and growth factors. This dynamic niche engages in reciprocal signaling with cancer cells, profoundly influencing tumor initiation, growth, metastasis, and therapeutic responsiveness.

NFCR-Supported Researchers Working on Tumor Microenvironment

Rakesh K. Jain

Rakesh K. Jain, Ph.D.
Massachusetts General Hospital

Kornelia Polyak Portrait

Kornelia Polyak, M.D., Ph.D
Dana-Farber Cancer Institute and Harvard Medical School

Valerie M. Weaver, Ph.D
University of California San Francisco

Aaron N. Hata, M.D., Ph.D.
Harvard Medical School and
Massachusetts General Hospital

Lisa Coussens, Ph.D.
Oregon Health & Science University

Elana Fertig, Ph.D
Johns Hopkins University
Sidney Kimmel Comprehensive Cancer Center

Daniel D. Von Hoff, M.D., FACP
Translational Genomics Research Institute (TGen)

Related Content

NFCR Fellow’s Research Sheds Light on Mechanism for Blood Vessel Formation in Cancer

Almost all living things need oxygen to survive. In human cells, the key to staying healthy is the right balance of oxygen. NFCR fellow Xiang-Lei Yang a professor at Scripps Research Institute has spent much of her career exploring the processes by which tumors sprout new blood vessels when they are oxygen-starved, a process known as angiogenesis. Dr. Xiang-Lei Yang, and NFCR-funded scientist Dr. Paul Schimmel, are worldwide experts in aminoacyl-tRNA synthetases (aaRS). aaRS is a family of enzymes that catalyze the synthesis of proteins from tRNA. While aaRS’s are best known for their role in protein synthesis, Dr. Yang discovered that a particular aaRS, SerRS, also plays a role in inhibiting angiogenesis. Prior angiogenesis research suggests that two genes — c-Myc and HIF-1 — are responsible for promoting blood vessel growth in healthy cells and tumors alike. As such, the turning on and transcription of these genes can promote tumor oxygenation and growth. In particular, c-Myc is one of the most important cancer-causing genes upregulated in many types of cancer. It also controls the gene for the production of VEGF, a blood vessel growth factor. In addition to its role in protein synthesis, SerRS limits blood vessel growth by inhibiting the function of the c-Myc and HIF-1. In the study published in PLOS Biology (December 2020), Yang and her fellow researchers share the discovery that during hypoxia, or oxygen starvation, proteins known as ATM/ATR are activated. The ATM/ATR protein activation “silences” or inhibits SerRS and promotes the formation of new blood vessels. Additionally, in separate studies of mice and human breast tissue, the researchers were able to display that ATM/ATR activation had a blocking effect on SerRS and resulted in reduced tumor size. In researching the role of ATM/ATR activation, and SerRS in breast cancer, Dr. Yang’s team found that the expression of SerRS is positively correlated with a greater rate of survival in breast cancer patients. Also, SerRS is significantly downregulated when metastasis, or cancer spread, occurs. Similar findings have been made in several other cancer types including brain, esophageal, kidney (clear cell), rectal, stomach, and thyroid cancers. These findings suggest that SerRS can inhibit the growth and metastasis of certain cancers and that ATM/ATR activation can counter that inhibition. These discoveries, funded in part by the National Foundation for Cancer Research, are core to our understanding of why and how tumors form new blood vessels and metastasize. As such, these discoveries may lead to novel therapeutic approaches that seek to limit ATM/ATR activation.

Angiogenesis

A vital process in growth and development but also plays a role in disease