Scientists discover the origins of metastasis

Date:
March 9, 2022
Source:
Universite' de Gene`ve
Summary:
Metastatic cells form in a primary tumor and then break
away from it, migrate to other organs, attach to them and
form new tumors. This spread reduces patients' chances of
recovery. Scientists have discovered some of the mechanisms by which
these cells arise. This is due to cells that have narrowly escaped
cell death (apoptosis) following a chemotherapeutic treatment. Those
cells reprogram themselves to acquire metastatic skills.

Thanks to this study, these cells - called PAME by the researchers -
now appear as new therapeutic targets.



FULL STORY ========================================================================== Metastatic cells form in a primary tumour and then break away from it,
migrate to other organs, attach to them and form new tumours. This spread reduces patients' chances of recovery. Scientists at the University of
Geneva (UNIGE) have discovered some of the mechanisms by which these
cells arise. This is due to cells that have narrowly escaped cell death (apoptosis) following a chemotherapeutic treatment. Those cells reprogram themselves to acquire metastatic skills. Thanks to this study, these
cells -- called PAME by the researchers -- now appear as new therapeutic targets. These results can be read in the journal Cell Reports.


========================================================================== Metastatic cells occur in many forms of cancer. They originate in primary tumours and then break away and migrate. They travel through the tissues surrounding them, through blood vessels or lymphatic channels. Along the
way, they may attach to one or more organs -- such as the lungs, brain,
bones or liver -- and form new tumours also called metastases. This spread
of the disease can negatively affect a patient's chances of recovery.

Previous studies have identified metastatic cells during migration. It is
also known that certain treatments can induce them. However, the precise mechanisms of their development remain a mystery. "We don't know why,
at a given moment, certain cells separate from the primary tumour,"
explains Ariel Ruiz i Altaba, a Full Professor in the Department of
Genetic Medecine and Development at the UNIGE Faculty of Medicine. "The phenomenon is difficult to analyze because, before they migrate, there
is nothing to distinguish future metastatic cells, or pro-metastatic
cells, from other cells within the tumour." Cells that should have died Professor Ruiz i Altaba's team composed of two postdocs for this study,
Arwen Conod (first author) and Marianna Silvano, has now provided some
answers.

Thanks to a recent research, these UNIGE scientists have discovered
that the experience of imminent death within the primary tumour
pushes certain cells to acquire pro-metastatic states. This near-death experience occurs in particular in the context of certain treatments
aimed at depriving cancer cells of energy or oxygen. The team observed
that these cells, which should have died, reprogram themselves and
then present a high metastatic risk. These cells are called PAME for "post-apoptotic pro-metastatic cells." A storm of cytokines To reach
these conclusions, the UNIGE team used tumour samples taken from two colon cancer patients. Tumour cells from these samples were then transplanted
into mice, where they grew and formed new tumours. These cells were
subjected to an imminent death experience causing endoplasmic reticulum
stress similar to that caused by certain chemotherapeutic drugs. This
allowed the development of PAME cells.

The scientists also discovered that PAMEs trigger a storm of cytokines -
- proteins and other factors that ensure cell-to-cell communication --
inducing adjacent cells to become PIMs, for PAME-induced migratory
cells. These PIMs then associate with PAMEs and help them migrate to
form metastases.

The present results open up promising new prospects for therapeutic
management, including the prevention of the development of pro-metastatic fields generated by certain treatments. "Currently, one of the main
criteria when defining a treatment is tumor shrinkage. Thanks to our
study, PAME cells now appear as potential therapeutic and metastasis
prevention targets to be taken into account," concludes Professor Ruiz
i Altaba.


========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Arwen Conod, Marianna Silvano, Ariel Ruiz i Altaba. On the origin of
metastases: Induction of pro-metastatic states after impending
cell death via ER stress, reprogramming, and a cytokine storm. Cell
Reports, 2022; 38 (10): 110490 DOI: 10.1016/j.celrep.2022.110490 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220309104441.htm

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