Metastasis from the tumor interior and necrotic core formation

Good news! Cancer is history (soon)!

"...New research ... shows that a tumor’s necrotic core — a mass of dying and dead cells previously thought to be inconsequential or perhaps even beneficial — contains factors that appear to promote metastasis, or the seeding of tumors cells throughout the body. ...

Metastatic, or stage 4 cancers, are treatable but still not curable. ... by better understanding the process of metastasis itself.

Tumor necrotic cores are a fairly common phenomenon ... but they haven’t been linked to cancer metastasis until recently. ...
“Our work shows a pretty direct link between necrosis, circulating tumor cells and cancer metastasis.” ..." 

From the significance and abstract:

"Significance

Aggressive tumors often die from the inside out, a process called necrotic cell death. Necrosis is associated with dissemination of cancer cells but how necrosis promotes tumor dissemination is not understood. Here, we used rats as a model organism to increase detection of dissemination events. This uncovered a sharp rise in circulating tumor cell (CTC) abundance associated with necrosis and changes in the blood vessels. Gene expression analysis revealed a tumor-derived gene program involved in shaping the tumor core ecosystem. We demonstrate that necrosis, vascular remodeling, and metastatic dissemination are dependent on a tumor-secreted factor, angiopoietin-like 7 (Angptl7). Understanding the molecular factors regulating metastatic dissemination from the necrotic core could unveil therapeutic strategies to treat and prevent metastatic cancers.

Abstract

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core."

Dead to me? Insights into a tumor’s necrotic core Research from Cheung Lab reveals role for ‘dead zone’ within cancers as a launch system for metastatic spread

Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7 | PNAS (open access)

Fig. 2 Angptl7 is a tumor-derived, necrotic core-enriched transcript localized to the perinecrotic region of breast tumor.