Going the distance--insights into how cancer cells spread

February 12, 2021

Most tumors consist of a heterogenous mix of cells. Genetic mutations found only in some of these cells are known to aid with the spread and progression of cancer. However, oncologists often find that when tumors metastasize to distant organs, they retain this heterogenous nature--a phenomenon termed "polyclonal metastasis". The mechanism by which non-metastatic cells accompany the metastatic cells is ambiguous. Now, Masanobu Oshima and his research team have used mouse models to explain how non-metastatic cells begin their long commute.

The team has previously developed various cancerous mutants of mice and analyzed them closely to reveal which cancer cells inherently spread and which do not. It was found that cells with four mutations, colloquially termed AKTP, were the most fatal. When these cells were transplanted into the spleens of mice, they migrated to and formed colonies in the livers within 3 days. In contrast, cells with two mutations, AK and AP, could not traverse this distance. To replicate polyclonal metastasis, AP cells were then co-transplanted with AKTP cells, and voila, both cell types indeed moved into the livers. Instead, when AP cells were injected into the blood (without prior exposure to the AKTP cells) they could not metastasize. Certain processes seemed to be at play when the cells were incubated together.

Next, AKTP cells within the liver tumors were killed to see how closely that affected the AP cells. The AP cells continued thriving and grew into larger tumors suggesting they did not need the AKTP cells anymore. Thus, at some point in the journey from the spleen to the liver the AP cells turned dangerous. To identify this point, the researchers traced back the chain of events. Within a day after transplantation, AKTP clusters were found in the sinusoid vessel, a major blood vessel supplying the liver. By 14 days, this cluster transformed into a mass termed as a "fibrotic niche". The same mass was observed with a mix of AP and AKTP cells, but not with AP cells alone. What's more, within this mass AKTP cells were activating hepatic stellate cells (HSCs). HSCs are responsible for scarring of liver tissue. Activated HSCs then set up the perfect environment for AP cells to proliferate infinitely. Harboring the AP cells within the fibrotic environment was, therefore, a key step.

"These results indicate that non-metastatic cells can metastasize via the polyclonal metastasis mechanism using the fibrotic niche induced by malignant cells," conclude the researchers. Targeting this fibrotic niche might be a promising strategy to keep the spread of solid tumors in check.
-end-


Background


Polyclonal metastasis: Solid tumors such as breast and colorectal cancer are famous for spreading notoriously. These tumor cells break off from the point of origin and migrate via the bloodstream into distant organs to set up shop. It is often found that such metastatic tumors are genetically diverse in nature. However, the role of cancer mutations in conferring tumors metastatic is still unclear. Older theories have suggested that genetic alterations are the sole key to turning cells metastatic. However, the study depicted here shows that other mechanisms are also at play.

Hepatic stellate cells (HSCs) and the fibrotic niche: HSCs are specialized cells of the liver responsible for scarring and wound healing mechanisms when activated. Upon activation, (after events such as liver damage) HSCs start proliferating and induce fibrotic tissue within the liver. Thus, their activation by AKTP cells resulted in development of the fibrotic niche, an environment particularly favorable for tumor proliferation.

Kanazawa University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.