How tumors transform blood vessels

The previously unknown role of tissue tension.

Share

Tracks rich in extracellular matrix (ECM) and different cells, also known as tumor matrix tracks, are found in various tumors. However, their morphological origin and roles remain unknown. They are high in tenascin-C (TNC) and other ECM molecules and have been found in various tumor types. 

These pathways appear to arrange tumors into tumor cell nests and interdigitating stroma. TNC-containing matrix-rich structures in tumors include tumor-associated collagen signatures 3 (TACS3) and reticular fibers in the spleen, lymph nodes, and thymus.

Over ten years ago, researchers discovered that tumors in various cancers, including colorectal cancer, breast cancer, and melanoma, have channels leading from the surface to the inside of the cell cluster. Yet, it has long been a mystery how these channels originate and what functions they perform.

These channels, dubbed tumor tracks by the researchers, were originally blood vessels but are now stripped of their original function of transporting blood.

These blood vessels begin by supplying glucose and oxygen to the rapidly growing cell clusters. But still, the vessels then go through a process that deprives them of their original function of blood transport: the vessel walls change, and the vessel cavity gradually fills up.

Researchers at ETH Zurich discovered that the tension of extracellular matrix fibers is essential in tumor development. Fibronectin fibers are extremely taut in healthy tissue but slack in tumor tissue. This more relaxed shape, surrounded by transformed blood channel walls, creates a space for cancer cells to grow undisturbed.

This filler material mainly comprises cells and newly formed protein fibers comprising the extracellular matrix.

Collagen and fibronectin fibers can be found here. The latter are involved in growth processes that occur mostly during embryonic development and wound healing. The researchers demonstrate in their external page article that the fibers within the tumor tracks can trap immune cells while the immune cells stretch out along the channels and stick to the loose fibronectin fibers. 

Vogel said, “In this elongated form, the immune cells switch from fighting diseases to supporting healing processes.”

It excretes molecules that stimulate growth, thus helping the cancer cells to multiply. 

She also said. “The extracellular matrix was frequently overlooked. That’s why the crosstalk between cells and their environment still remains a mystery. But if you want to understand what a spider does, you also have to look at its web. The main focus of cancer research has been on the cells.” 

She said, “The better we understand how the microenvironment steers how tumor cells multiply, the likelier it is that we’ll find a way of preventing them from doing so.” 

Vogel cautions about translating the findings to people because they are based on trials on mice with breast cancer. It needs to be explored whether or not these findings can be directly applied to human tumors. But, as Orend’s group external page recently demonstrated all made, there are significant analogies.

Vogel’s research group is collaborating with the Kantonsspital Baden on a follow-up project to investigate if tissue samples from breast cancer patients also contain traces of converted blood vessels. 

Researcher said. “We’re curious to discover where we’ll find similarities and where we’ll see differences,” 

Journal References:

  1. Fonta, C. M., Loustau, Poilil Surendran, etal. Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low-tension fibronectin fibers. Matrix Biology. DOI: 10.1016/j.matbio.2023.01.002
  2. Murdamoothoo D, Sun Z, Yilmaz A, etal. Immobilization of infiltrating cytotoxic T lymphocytes by tenascin-C and CXCL12 enhances lung metastasis, EMBO Molecular Medicine. DOI: 10.15252/emmm.202013270

Newsletter

See stories of the future in your inbox each morning.

Trending