The Multifaceted Role of Mast Cells in Cancer
Mast cells may play an important role in cancer.
They are potential triggers of allergic reactions, so stabilising them has long been a therapeutic target in treating allergies, asthma, and anaphylaxis.
It is time to shift attention to the role mast cells play in cancer and how we might use this understanding for therapeutic advantage.
Mast cells originate in the bone marrow and enter the circulation in immature form.
Once settled into a tissue site, they mature, taking on characteristics specific for that tissue.
There are two general types of mast cells: those found in connective tissue and those found in mucosal tissue.
We usually think of mast cells in association with boundary areas, such as the skin, but especially the mucosa of the lungs, digestive tract, mouth, nose, and eyes.
One image of mast cells is a cross between a sentry and a land mine posted around our perimeter.
When triggered by antigens, they degranulate, releasing destructive enzymes and sounding chemical alarms that cause a series of chain reactions resulting in acute allergic inflammation.
Often our therapeutic intent is to decrease allergen-triggered reactions.
In a paper titled, “The role mast cells have in tumour growth,” Conti, Castellani, and colleagues point out that many tumours are surrounded by mast cell infiltrates. They present evidence that these mast cells secrete inflammatory cytokines that sometimes benefit the cancer. Once mast cells are attracted to tumours by chemo-attractants like Stem Cell Factor, they are then triggered to secrete molecules that act as growth factors aiding tumour growth, angiogenesis, and metastasis. The mast cells ‘remodel’ the tumour microenvironment to promote tumour growth. This increases secretion of inflammatory chemicals, increasing activity of NF-kappaB and increasing the tumour’s ability to suppress T cell and natural killer cell attacks against it.
In their 2009 paper, the Italians Ribatti and Crivelatto suggest that mast cells could be a target for cancer treatment. Citing evidence that mast cells appear to play a significant role in tumour angiogenesis, they write, “In tumour models, mast cells have been shown to play a decisive role in inducing the angiogenic switch which precedes malignant transformation. There is, moreover, strong evidence that mast cells significantly influence angiogenesis and thus growth and progression in human cancers.” It would appear that if we could decrease mast cells we might inhibit both tumour angiogenesis and tumour growth.
Conti P, Castellani ML, Kempuraj D, et al. Role of mast cells in tumor growth. Ann Clin Lab Sci. 2007;37(4):315-322.
Huang B, Lei Z, Zhang GM, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood. 2008;112(4):1269-1279.
Ribatti D, Crivellato E. The controversial role of mast cells in tumor growth. Int Rev Cell Mol Biol. 2009;275:89-131.
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