How prostate cancer cells mimic bone when they metastasize

Prostate cancer often becomes lethal as it spreads to the bones, and the process behind this deadly feature could potentially be turned against it as a target for bone-targeting radiation and potential new therapies.

Study published online in the journal PLOS ONE, Duke Cancer Institute researchers describe how prostate cancer cells develop the ability to mimic bone-forming cells called osteoblasts, enabling them to proliferate in the bone microenvironment.

Attacking these cells with radium-233, a radioactive isotope that selectively targets cells in these bone metastases, has been shown to prolong patients' lives. But a better understanding of how radium works in the bone was needed.

The mapping of this mimicking process could lead to a more effective use of radium-233 and to the development of new therapies to treat or prevent the spread of prostate cancer to bone.

"Given that most men who die of prostate cancer have bone metastases, this work is critical to helping understand this process," said lead author Andrew Armstrong, Director of Research at the Duke Cancer Institute Center for Prostate and Urologic Cancers.

The research team enrolled a small study group of 20 men with symptomatic bone-metastatic prostate cancer. When analyzing the circulating tumor cells from study participants, they found that bone-forming enzymes appeared to be expressed commonly, and that genetic alterations in bone forming pathways were also common in these prostate cancer cells.

They validated these new genetic findings in a separate multicenter trial involving a larger group of more than 40 men with prostate cancer and bone metastases.

Following treatment with radium-223, the researchers found that the radioactive isotope was concentrated in bone metastases, but tumor cells still circulated and cancer progressed within six months of therapy. The researchers found a range of complex genetic alterations in these tumor cells that likely enabled them to persist and develop resistance to the radiation over time.

"Osteomimicry may contribute in part to how prostate cancer spreads to bone, but also to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy," Armstrong said.

He said by mapping this lethal pathway of prostate cancer bone metastasis, the study points to new targets and thus critical areas of research into designing better tumor-targeting therapies.

An important announcement regarding our upcoming conference 12^th World Congress on Cell & Tissue Science (Cell Tissue Science 2019) scheduled on September 13-14,2019 in Singapore. You can also present your latest research at the different topics such as Cancer Cell Biology, Stem Cell & its applications and many more along with other distinguished professors, doctors and researchers from all over the world.

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New methods to identify AD drug candidates with anti-aging properties

Long thought to suppress cancer by slowing cellular metabolism, the protein complex AMPK also seemed to help some tumors grow, confounding researchers. Now, Salk Institute researchers have solved the long-standing mystery around why AMPK can both hinder and help cancer.

The lab of Salk Professor Reuben Shaw showed that late-stage cancers can trigger AMPK's cellular recycling signal to cannibalize pieces of the cell, supplying large lung tumors with the nutrients they need to grow. The work was published in  Cell Metabolism suggests that blocking AMPK in some conditions could stop the growth of advanced tumors in the most common type of lung cancer.

"Our study shows that the same dysfunction in a genetic circuit that causes non-small-cell lung cancer to begin with is necessary for more mature tumor cells to survive when they don't have enough nutrients," says Shaw, Director of the Salk Cancer Center. "It's exciting because not only does it solve a genetic 'whodunnit,' but it also points to a potential new therapeutic target for a cancer that is often diagnosed very late."

AMPK acts as a fuel gauge for the cell, overseeing energy input and output to keep the cell running smoothly. Similar to a car sensor flashing a low-gas signal or turning off a vehicle's AC to save energy, AMPK slows down cell growth and changes the cell's metabolism if the cell's fuel (nutrients) is low. Previously, Shaw discovered that AMPK could halt tumors' revved-up metabolism, as well as restore normal function to the liver and other tissues in diabetics.

"We found that tumors grew much more slowly when AMPK was not present," says Research Associate Lillian Eichner."That means that AMPK is not always functioning as a tumor suppressor, as we originally thought."

The team analyzed which genes in tumor cells from the same mouse models were being activated under various conditions. One gene that was particularly active was Tfe3, which is known to activate cellular recycling. It turned out that when tumors became large enough that cells in the middle were too far from easy access to nutrients, AMPK signaled Tfe3 to initiate recycling of cellular materials as nutrients--effectively cannibalizing pieces of the cell--for the tumor to use.

"Previously we were focused on how we could activate AMPK," says Eichner. "Now that we've identified this mechanism, we can shift to how to inhibit it in certain cancers."

Shaw, who holds the William R. Brody Chair, adds, "We're excited because more advanced tumors seem to rely on AMPK to survive, and understanding this mechanism means we may be able to treat them."

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatmentand many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

You can submit your abstract on Session or Track : 16.Anti-Aging Medicine

Combining genetic and sun exposure data improves skin cancer risk estimates

By combining data on individuals' lifetime sun exposure and their genetics, researchers can generate improved predictions of their risk of skin cancer.

Pierre Fontanillas, PhD, and colleagues at 23andMe, Inc., collected genetic and survey data from over 210,000 consented research participants of European descent. They analyzed the data to identify correlations between previously known and potentially novel skin cancer risk factors and the occurrence of three forms of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Past studies had found that exposure to ultraviolet (UV) light increases skin cancer risk, as do other environmental factors such as living in a sunnier climate or at a higher altitude, and personal factors such as lighter skin pigmentation, higher numbers of moles on the skin, and family history of skin cancer.

"We aimed to validate previously known skin cancer risk factors in a large cohort, add detail to these and explore potential new ones, and find out whether and how these factors might interact with genetic risk," said Dr. Fontanillas.

They found that while each single factor was not particularly significant on its own, multiple factors could be combined into statistical models that were more informative. The best-performing models incorporated a genetic risk score composed of data on up to 50 genetic variants, along with survey data on family history, skin pigmentation and sensitivity, number of moles, estimated current sun exposure, sunbathing frequency before the age of 30, and body mass index (BMI).

The new models achieved a high predictive accuracy (area under the curve [AUC], between 0.81 and 0.85). Genetic factors alone accounted for 8.3 to 15.2 percent of the variance explained in skin cancer risk. Although the three skin cancers have different physiology, models did not find fundamental differences between the three cancer types, nor did they show strong interaction between genetic and environmental risk factors. While the self-reported nature of the survey data permitted researchers to collect a large dataset, it also presented some challenges, Dr. Fontanillas noted.

"Measuring lifetime exposure is generally challenging. It is particularly hard to capture sun exposure and when in life it happened, and it may be that some of the other correlates we found, like higher BMI, reflect a lack of outdoor activity rather than being directly correlated with risk of skin cancer," he said.

Moving forward, the researchers plan to expand their sample to groups with non-European ancestry and are exploring additional methods of calculating genetic risk score and measuring sun exposure. They hope to eventually obtain risk estimates accurate enough to be used by individuals and clinicians.

We welcome researchers from different part of the world to submit your latest research at our upcoming conference "12th World Congress on Cell & Tissue Science" scheduled on March 11-12,2019 in Singapore which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more. For more info visit our conference website:Cell Tissue Science 2019