La différenciation entre cellules souches saines et cancéreuses.

(Nov. 2, 2012) — A new tool developed by scientists at The Methodist Hospital separates tumor-causing cancer cells from more benign cells by subjecting the cells to a microscopic game of Plinko -- except only the squishiest cells make it through.

Un nouvel outil développé par les scientifiques sépare les cellules qui cause le cancer des cellules plus saines en les soumettant à une sorte de jeu de Plinko, sauf que c'est seulement les cellules qui peuvent facilement se déformer qui passent au travers.

As reported in this week's Proceedings of the National Academy of Sciences (early edition online), the more flexible, tumor-causing cells navigated a gamut of tiny barriers, whereas the more rigid, more benign cells had trouble squeezing through 7 micrometer holes. Methodist scientists worked with University of Texas MD Anderson Cancer Center researchers to test the device with different kinds of cancer cells.

Les cellules passent par des trous de 7 micromètres, les cellules rigides ont de la difficulté et les plus amolissantes réussisent.

The work supports the hypothesis that cell squishiness indicates tumor potential. Most normal cells contain a developed cytoskeleton -- a network of tiny but strong rod-shaped proteins that give cells their shape and structure. In their feverish drive to divide, cancer cells may be diverting resources away from developing a cytoskeleton in favor of division, hence the squishiness.

Ces cellules plus molles sont celles qui ont perdu leur partie dure et qui sont plus susceptibles d'être celles qui sont les cellules souches cancéreuses.

"We have created many pathways for cells to cross barriers," said Methodist nanomedical faculty Lidong Qin, Ph.D., the project's principal investigator. "The throughput of a MS-Chip is at the level of one million cells. When a stiff cell blocks one particular barrier, many other bypasses will allow flexible cells to flow through."

Cancer stem cells are known to be squishier than other cancer cells. The team of scientists showed that flexible cells separated by the MS-Chip exhibited gene expression patterns consistent with cancer stem cells.

"Many papers indicate the presence of cancer stem cells means a worse prognosis for patients," said cancer scientist Jenny Chang, M.D., co-principal investigator and director of Methodist's Cancer Center. "Yet they are not typically quantified by doctors."

Cela veut dire un mauvais pronostic lorqu'il y a des cellules souches cancéreuses.

Subsequent analysis of separated cells by the Methodist and MD Anderson team showed the flexible cells were less likely to express cell cytoskeleton genes and more likely to express the motility genes that could contribute to metastasis.

plus suceptibles de métatstaser également

By testing for the presence of metastatic cells, doctors may be able to tell whether cancer treatment was successful, or an as-yet untreated cancer's likelihood of metastasizing to another part of the body.

A growing awareness of cancer stem cells' role in cancer metastasis and recurrence and has been frustrated by the absence of technology that makes this knowledge useful to doctors and their patients. Up to now, there has been no way of quickly and reliably separating and identifying the more dangerous tumor-causing cells from a biopsy.

The new device, which was developed at Methodist, successfully enriched tumor-causing cells from a mixture of cancer cells. It is called the Mechanical Separation Chip, or MS-Chip. Cells separated by the device can be easily collected and studied. The current standard for cell separation, flow cytometry, is relatively slow and relies on cell surface biomarkers.

les cellules récoltés par cet outils peuvent être plus rapidement étudiées. L'outil standard pour cela est plus lent.

"Our microfluidics cell separation via MS-Chip provides a high throughput method that can particularly sort cells to different levels of stiffness, which opens a new avenue to study stiffness related cellular and molecular biology," Qin said. "Downstream molecular analysis, including genomic and proteomic profiling of the cell subtypes, provides an approach to identifying new biomarkers relevant to cancer stem cells and cancer metastasis."

Right now, each MS-Chip costs about $10 to produce.

"If massively produced, MS-Chip cost could be at the level of one dollar per chip," Qin said. "Running a mechanical cell separation will be even less expensive than flow cytometry cell sorting."

(Jan. 9, 2009) — One of the current handicaps of cancer treatments is the difficulty of aiming these treatments at destroying malignant cells without killing healthy cells in the process. But a new study by McMaster University researchers has provided insight into how scientists might develop therapies and drugs that more carefully target cancer, while sparing normal healthy cells.

Un des handicaps des traitements du cancer c'est la difficulté à cibler les traitements sur les cellules cancéreuses en évitant les cellules saines dans le processus. Mais une nouvelle étude démontre comment les scientifiques peuvent développer des thérapies et des médicaments qui ciblent plus soigneusement le cancer en épargant les cellules saines.

Mick Bhatia, scientific director of the McMaster Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine, and his team of investigators have demonstrated – for the first time – the difference between normal stem cells and cancer stem cells in humans.

Mick Bhatia démontré pour la première fois la différence entre une cellule souche cancéreuse et une normale chez l'humain.

The discovery, published in the journal Nature Biotechnology January 4, could eventually help with the further customization and targeting of cancer treatments for the individual patient. It will immediately provide a model to discover drugs using robotic screening for available molecules that may have untapped potential to eradicate cancer.

La découverte aidera éventuellement à préparer des traitements individuels customisés et ciblés en fonction de chaque personne. Les outils informatiques et de la robotique aideront à définir ces traitements et médicaments.

“Normal stem cells and cancer stem cells are hard to tell apart, and many have misconstrued really good stem cells for cancer stem cells that have gone bad - we now can tell the ones masquerading as normal stem cells from the bad, cancerous ones,” said Bhatia.

“This also allows us to compare normal versus cancer stem cells from humans in the laboratory - define the differences in terms of genes they express and drugs they respond to. Essentially, we can now use this to find the “magic bullet”, a drug or set of drugs that kill cancer stem cells first, and spare the normal healthy ones,” he said.

Tout ceci nous permets de comparer les versions de cellules soucjes cancéreuses avec les saines et de définir les différences en terme de gènes qu'ils expriment et des médicaments pour répondre. Nous pouvons nous servir de ces nouvelles connaissances pour trouver la balle magique, un médicament qui tuerait les cellules souches cancéreuses tout en épargant les saines.

“McMaster is uniquely positioned for this discovery platform, and this was the missing ingredient - we have one of the best screening/robotic platforms, chemical libraries and expertise in professors Eric Brown and Gerry Wright, who have discovered molecules to combat infectious disease. Now we can combine it all. This team now aims to kill cancer.”

This work is funded by the Canadian Institutes of Health Research, the Canadian Cancer Society; the Ontario Institute for Cancer Research and the National Cancer Institute of Canada.