Navigation Links
Tumors form advance teams to ready lungs for spread of cancer
Date:8/15/2013

PHILADELPHIA Cancer metastasis requires tumor cells to acquire properties that allow them to escape from the primary tumor site, travel to a distant place in the body, and form secondary tumors. But first, an advance team of molecules produced by the primary tumor sets off a series of events that create a network of nurturing blood vessels for arriving primary tumor cells to set up shop.

In lung cancer, the formation of that niche likely involves immune cells and moderate levels of VEGF and other molecules that promote the formation of new blood vessels, or angiogenesis. But little is known about how the local lining, or endothelial, cells are activated at the niche.

Sandra Ryeom, PhD, assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, and colleagues, found that the signaling protein calcineurin upregulates another molecule, Ang-2 that promotes the needed angiogenesis. Hyperactivation of calcineurin in genetically altered mice that lack an inhibitior of calcineurin signaling leads to increased lung metastases. Conversely, inhibiting calcineurin or Ang-2 blocked metastases in lung cells of the mice. The findings are published this week in Cell Reports.

The findings may help shed light on the underpinnings of common cancer metastasis patterns, such as the tendency of prostate cancer to spread to the bones, or melanoma to the brain.

"We demonstrated that the calcineurin pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially and spontaneously metastasize to the lung from our experimental model of flank tumors in mice," says Ryeom.

Also, increased VEGF levels specifically in the lung, and not other organ microenvironments, trigger a threshold amount of calcineurin signaling that activates the Ang2 gene in lung endothelial cells. What's more, they showed that overexpression of the Ang-2 receptor prevents activation of the lung endothelium and inhibits lung metastases in their mouse models.

"Our studies provide insights into the mechanisms underlying angiogenesis in the pre-metastatic niche and offer new targets for lung metastases," she says.

Because calcineurin acts on the pathways that set up sites of metastasis away from the primary tumor sites, it could be a potential target for future cancer therapies; however it is also active in the immune system. In fact, calcineurin is inhibited by cyclosporine, which is used to combat transplant rejection, so using these types of drugs would be tricky for cancer unless they can be targeted specifically towards endothelial cells.

Ongoing studies in the Ryeom lab are investigating whether calcineurin is important for metastases in other organs or whether this pathway is specific for lung metastases.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Carbon ion radiotherapy safe and effective for treating inoperable spinal tumors
2. Suffocating tumors could lead to new cancer drugs
3. Protein complex linked to cancer growth may also help fight tumors, Moffitt researchers say
4. Voices Against Brain Cancer Comments on Discovery of Nano Drug That May Aid in Treatment of Brain Tumors
5. Compounds outsmart solid tumors malfunctioning machinery
6. Suspicions confirmed: Brain tumors in children have a common cause
7. Therapy that heats and destroys bone tumors eases patients pain
8. New drug improves progression-free survival, shrinks tumors in rare cancer for first time
9. Many solid tumors carry genetic changes targeted by existing compounds
10. Immune system to fight brain tumors
11. Modified Polio Virus May Help Fight Brain Tumors, Study Suggests
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that covers ... companies have a waiver for care if the client has a cognitive impairment diagnosis. ... pays for care, is often waived, so the benefits from their insurance start immediately,” ...
(Date:10/13/2017)... ... , ... Talented host, actor Rob Lowe, is introducing a ... episode of "Success Files," which is an award-winning educational program broadcasted on PBS ... in-depth with passion and integrity. , Sciatica occurs when the sciatic nerve in ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... sleep apnea using cutting-edge Oventus O2Vent technology. As many as 18 ... characterized by frequent cessation in breathing. Oral appliances can offer significant relief to ...
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... Chapel, FL (PRWEB) , ... October 12, 2017 , ... ... is holding a treadmill relay – Miles by Moonlight to raise money for the ... donating $300 or more. , Teams will work together to keep their treadmills ...
Breaking Medicine News(10 mins):
(Date:10/10/2017)... Pa. , Oct. 10, 2017   West ... in innovative solutions for injectable drug administration, today shared ... West,s ID Adapter for improving the intradermal administration of ... Fourth Skin Vaccination Summit in May 2017 by Dr. ... Lead, Polio Department, World Health Organization (WHO), and recently ...
(Date:10/4/2017)... 2017  South Korean-based healthcare product Development Company I.M. ... on Kickstarter. The device will educate the user about ... better efficiency compared to the dated and pricey CPR ... efficacy of the compression for a more informed CPR ... to raise $5,000. ...
(Date:10/2/2017)... -- Diplomat Pharmacy, Inc. (NYSE: DPLO ) ... , and named its founder as Diplomat,s chief information ... Tennessee , will operate under Diplomat subsidiary Envoy ... for health care partners to include IT outsourcing, consulting, ... "In an interoperable world, technology delivers comprehensive insight and ...
Breaking Medicine Technology: