Researchers have taken a major step toward answering a key question in cancer research: Why is testicular cancer so responsive to chemotherapy, even after it metastasizes?
Professional cyclist Lance Armstrong, for example, had testicular cancer that spread to his lung and brain, yet he made a full recovery after conventional chemotherapy.
The key to such success appears to lie in the cancer's stem cells, which are more sensitive to chemotherapy than stem cells found in other types of cancer. Defining why testicular cancers are so susceptible to chemotherapy could eventually provide insights for treating other, more resistant cancers.
The group's study, published in the journal Cell Reports, also helped confirm that risk for testicular cancer is determined in utero. The research offers some evidence to support a hypothesis that, in humans, testicular cancers are initiated during embryonic development and lay dormant for 18 to 35 years.
"The study provides new insights into the basis for the responsiveness of testicular cancer to chemotherapy, which has always been an intriguing observation, but the basis for it was not clear," said senior author of the study.
Most types of tumors contain distinct populations of cells. A small fraction of these are stem cells, which have the ability to grow new tumors from a single cell and - in most cancers - are extremely resistant to therapy. Often, other types of tumor cells are killed off during treatment, but cancer stem cells survive, then drive relapse by re-growing new tumors.
But "when testicular cancer stem cells are exposed to chemotherapy, those stem cells are actually more sensitive to it than other cells in the tumor," senior author said.
In the study researchers created a mouse model that, for the first time, can accurately mimic the properties of testicular cancers found in humans. In particular, the engineered mice used in the study develop cancers with the strongest expression of stem cell markers reported to date. The mouse model accurately duplicates realistic tumor characteristics, such as the rate of tumor growth and the ability to give rise to several different tumor cell types.
While other cancers are known as diseases of the elderly, testicular cancers generally strike between the ages of 18 and 40, with rates dropping in older men. Using the mouse model, the researchers reported that germ cells become susceptible to developing into testicular cancer only during a restricted period of embryonic development. As they age, they become resistant to transformation.
In the mouse model, the researchers found that genetic risk factors can make embryonic germ cells malignant, but when adult germ cells are exposed to the same conditions, those cells die instead of giving rise to a tumor.
"This observation aligns well with human epidemiological data and leads to a number of intriguing questions about what makes embryonic germ cells vulnerable to developing into cancer and how adult germ cells can fend off the same challenges," senior author said.
Future work may provide clues for treating other cancers if researchers can identify what features of the testicular cancer stem cells make them responsive to chemotherapy and compare those features in other tumor types, senior author said.
http://www.cell.com/cell-reports/abstract/S2211-1247(17)31541-3
Latest News
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Cell's 'garbage disposal' h…
By newseditor
Posted 16 Apr
Other Top Stories
Mechanism of action of melanoma protein B-Raf
Read more
Leukemia detection using artificial intelligence
Read more
Protein interactions in kidney cancer
Read more
Brain tumor organoids may be key to time-sensitive treatments for g…
Read more
Importin protein transporting tumor causing catenin to the nucleus…
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Oligodendroglial macroautop…
By newseditor
Posted 17 Apr
COPII with ALG2 and ESCRTs…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar