Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Growth Signal Can Influence Cancer Cells’ Vulnerability to Drugs, Study Suggests


In a study published February 26, in Cell, researchers at Rockefeller University home in on one culprit that fuels this variable vulnerability within squamous cell cancers: exposure to a signal known as TGF-β, given off by immune cells that congregate next to a tumor’s blood vessels.

“There are several reasons why some cancer stem cells, the cells at the root of tumors and metastases, can withstand therapy meant to eradicate them. Our results point to the importance of the environment immediately surrounding the skin cancer stem cells, specifically, their exposure to the signal TGF-β,” says senior researcher Elaine Fuchs, Rebecca C. Lancefield Professor, head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development and a Howard Hughes Medical Institute Investigator.

Zach Veilleux

A cue for cancer: To see how exposure to the growth signal TGF-β influences cancer cells, the researchers used a red tag (top) to mark mouse tumor stem cells that received the signal, and a green tag (bottom) to track the behavior the stem cells’ progeny.

“Ultimately, we hope this new insight could lead to better means for preventing the recurrence of these life-threatening cancers, which can occur in the skin, head, neck, esophagus, and lung, and often evade treatment.”

Her team, which included first author Naoki Oshimori, a postdoctoral research associate in the lab and lab technician Daniel Oristian, focused on squamous cell carcinomas in the skin of mice. Like many normal tissue stem cells, the stem cells that produce squamous cell tumors can be classified into two types: those that divide and proliferate rapidly, and those that do so more slowly. This has led scientists to wonder whether the more dormant stem cells in a tumor might evade cancer drugs.

To investigate this possibility, the team zeroed in on TGF-β (transforming growth factor beta) which is known to restrict growth in many healthy tissues. The lab’s previous research has shown that mice whose normal skin stem cells cannot respond to TGF-β become susceptible to develop tumors that grow rapidly. Paradoxically, however, TGF-β contributes to metastasis in many cancers. The researchers wanted to know: How can TGF-β act both to suppress cancers and promote them?

By visualizing TGF-β signaling within developing mouse tumors, the researchers found that the cancer stem cells located nearest to the blood vessels of the tumor receive a strong TGF-β signal, while others further away don’t receive any. To see this difference and its effects, they used a red tag to illuminate those cells exposed and responding to TGF-β, and a green genetic tag, which they could switch on, to track the stem cells’ progeny. Over time, they saw that TGF-β-responding stem cells proliferate more slowly but they simultaneously invade, scatter and move away from the tumor. The opposite was true of cancer stem cells too far away to receive TGF-β, which proliferated rapidly, but were less invasive, growing as a tumor mass.

“We tested the implications for drug resistance by injecting cisplatin, a commonly used chemotherapy drug for these types of cancers, into the mice with tumors. While the drug killed off most of the TGF-β nonresponding cancer cells, it left behind many of the responders,” Oshimori says. “When the drug was withdrawn, the lingering TGF-β responding cancer stem cells grew back the tumor.”

“We found that the TGF-β heterogeneity in the tumor microenvironment produces some cancers stem cells that divide rapidly and lead to accelerated tumor growth, and other cancer stem cells that invade surrounding healthy tissue and escape cancer therapies,” Fuchs explains. “Moreover, conventional wisdom might say that a leisurely pace of cell division, like that seen in the TGF-β responders, makes it possible for these cells to circumvent anticancer treatments that target rapidly dividing cells. While this may be true for some types of anticancer drugs, we found changes in antioxidant activity in these cells are more important for their resistance to cisplatin.”

Indeed, when the team compared the genes expressed by the TGF-β responders with those of the nonresponders, they found highly elevated expression in a battery of genes encoding enzymes involved in making and utilizing glutathione, an important antioxidant and detoxifying substance in cells. This unexpected finding led the team to test the impact of glutathione metabolism and conclude this metabolic pathway prevents TGF-β responders from critical damage by anti-cancer drugs as well as oxidative stresses.

“If TGF-β signaling and elevated antioxidant activity plays the same role predisposing cancer stem cells to thwart chemotherapy in humans as we have shown it does in mice, this work may serve as a foundation for designing new therapeutics and combinatorial regiments to overcome drug resistance by this devastating cancer,” Fuchs says.

Contact Information
Zach Veilleux

Zach Veilleux | newswise

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

VDI presents International Bionic Award of the Schauenburg Foundation

26.10.2016 | Awards Funding

3-D-printed magnets

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>