Breast cancer is the most commonly diagnosed cancer with the second leading cause of cancer death among women. However, breast cancer has the best prognosis if detected early. It is a well-known fact that cancer can be managed clinically unless it shows metastatic growth in other tissues. Metastases of primary breast tumor cells into secondary tissues leads to poor prognosis, especially after recurrence. Metastasis is a very complex phenomenon, which arises from uncontrolled proliferation of primary tumor cells leading to the production of circulating tumor cells. Certain tumors have more capabilities to break through the wall of a vessel while cancer like basal cell carcinoma (mostly benign) rarely invade through. These circulating tumor cells invade other tissues where they proliferate further and form the new observable clinical tumor. Most of the symptoms in cancer patients originate upon subsequent tissue invasion of primary tumor cells causing the reduced function of the affected organ.
A recently published paper in a reputed peer-reviewed Nature journal indicates that certain diet may not bode well for breast cancer metastasis. Authors from this study have shown previously that diverse primary breast tumor cells have different capabilities to become circulating tumor cells and form tumors at distant sites. Thus, indicating clonal nature of metastases of primary breast tumor cells. In the current study, authors went one step further to investigate the underlying mechanism of metastatic potential of these different clones of breast tumor cells. Using RNA interference screening methods, they found asparagine synthetase gene was one such candidate imparting metastatic capabilities to these invading breast tumor clones. Expression of this gene in patient primary tumor cells strongly correlated with more invading potential into secondary tissue sites. This gene regulates the availability of non-essential amino acid asparagine to the cells for building new proteins. Asparagine is rich in certain foods like asparagus, meats, poultry, dairy, seafood, potatoes, legumes, nuts, seeds, soy and whole grains while most fruits and vegetables are low in asparagine.
Authors of the present study showed the importance of asparagine in tumor invasion by knocking down asparagine synthetase using RNA interference (shRNA or siRNA) in triple negative breast cancer cell line derived from cancer patients. They did in-vitro invasion assay using matrigel to show that knockout cells have reduced capacity to invade tissues, unlike normal tumor cells. They also did experiment where forced expression of asparagine synthetase in tumor cell lines increased the metastatic potential of tumor cells without affecting the growth of primary tumor cells. Furthermore, by limiting the amount of asparagine amino acid in the diet of mice receiving human breast cancer cell lines, authors show that mice had more invasion with asparagine-rich food and fewer metastases score with low asparagine diet. High expression of asparagine synthetase correlates with poor prognosis of many different types of human cancers, thus indicating real implication of this study linking diet and cancer burden.
This study for the first time suggests how the bioavailability of a single amino acid could influence invasion capabilities of tumor cells.
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