Researchers uncover 'relocation' plan of metastatic cancer cells

January 5, 2009

Few things are as tiresome as house hunting and moving. Unfortunately, metastatic cancer cells have the relocation process down pat. Tripping nimbly from one abode to another, these migrating cancer cells often prove far more deadly than the original tumor. Although little has been known about how these rogue cells choose where to put down roots, researchers at the Stanford University School of Medicine have now learned just how nefarious they are.

"Metastasis is not a passive process," said cancer biologist Amato Giaccia, PhD. "Cells don't just break off the primary tumor and lodge someplace else. Instead the cells actually secrete substances to precondition target tissue and make it more amenable to subsequent invasion."

In other words, the cells plan ahead by first sending molecular emissaries to orchestrate a breach in the body's natural defenses. Blocking this cascade of events in mice hobbled the cells' migration and prevented the metastatic cancer that developed in control animals. The researchers are hopeful that a similar tactic will be equally successful in humans.

Giaccia, the Jack, Lulu and Sam Willson Professor and professor of radiation oncology at Stanford, is the senior author of the research, which will be published in the Jan. 6 issue of Cancer Cell. Giaccia is also a member of the Stanford Cancer Center.

Scientists have known for some time that certain primary cancers metastasize preferentially to other organs — breast cancer often spreads to the lungs, for example. This is in part due to the patterns of blood flow in the body. They also knew that such future colonization sites, called pre-metastatic niches, harbor large numbers of cells derived from the bone marrow that somehow facilitate the cancer cells' entry. What they didn't know is how the bone-marrow-derived cells were summoned, and what, if any, role the primary tumor cells played in site selection.

Giaccia and his colleagues turned their attention to a substance that they had previously shown to be involved in metastasis: a protein called lysyl oxidase, or LOX. In healthy people, LOX works to strengthen developing connective tissue by modifying collagen and elastin, which are components of the extracellular matrix surrounding many organs. LOX expression increases in cancer cells deprived of oxygen — a condition called hypoxia that begins to occur when blood vessels fail to reach the inner cells of a growing tumor mass. Inhibiting LOX expression decreases tumor cell invasion and metastasis in the lungs of mice implanted with human breast cancer cells.

The researchers wanted to know how LOX affected metastasis. In the current study, they found that blocking LOX expression in the mice not only prevented metastases, it also kept the bone-marrow-derived cells necessary for niche formation from flocking to the site. When LOX was present, it accumulated in the lungs of the mice and was associated with one particular type of bone-marrow-derived cell known as a CD11b cell. CD11b cells, in turn, secreted a protein that breaks apart collagen and provides a handy entry point for the soon-to-arrive cancer cells.

"We've never really understood before how normal tissues are modified to allow metastases to target and successfully invade them," said Giaccia, who is hoping to devise a clinical trial to study the effect of blocking LOX activity in humans with primary cancers. "Now we know that LOX goes to the target tissue and attracts CD11b and other bone-derived cells to the pre-metastatic niche. If the mouse data is transferable to humans, and we have reasons to think it will be, we really believe way may have found an effective way to treat human disease."

Source: Stanford University Medical Center

Explore further: Erlotinib overdose tied to conjunctivitis

Related Stories

Erlotinib overdose tied to conjunctivitis

November 19, 2017
(HealthDay)—Overdosing of erlotinib may be associated with rapid onset of conjunctivitis, according to a case report published online Oct. 25 in the Journal of Clinical Pharmacy and Therapeutics.

Team identifies protein key to cancer cells ability to spread

November 17, 2017
University of Guelph scientists have made a discovery that could reduce the spread of cancer by hindering a protein that binds cancer cells together and allows them to invade tissues.

Researchers identify potential therapeutic target in aggressive breast cancer cells

November 15, 2017
An especially aggressive breast cancer cell can respond to hormone therapy if they express a specific protein known as estrogen receptor beta (ERβ), according to new research published on the cover of Oncotarget. The findings ...

Harder for T cells to fight cancer in absence of VEGF-A

November 13, 2017
Contrary to what was previously believed, the immune system's cancer-killing T cells are more effective in a tumour's anoxic environment when they have access to growth factor VEGF-A. In a study from Karolinska Institutet ...

How a poorly explored immune cell may impact cancer immunity and immunotherapy

November 17, 2017
The immune cells that are trained to fight off the body's invaders can become defective. It's what allows cancer to develop. So most research has targeted these co-called effector T-cells.

New cancer cell screening is improving childhood leukaemia treatment

November 14, 2017
A study has shown that current methods used to determine the correct level of chemotherapy required for each young patient may be improved by looking at the genetic make-up of the child's cancer cells.

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.