This author interview is by Dr Ravi P. Sahu, of Indiana University School of Medicine.  Dr Sahu's full paper, Systemic Platelet-activating factor receptor activation augments experimental lung tumor growth and metastasis, is available for download in Cancer Growth and Metastasis.

First please summarise for readers the content of your article 

Pro-oxidative stressors that generate free radicals including ultraviolet B (UVB) and cigarette smoke (CS) are associated with the suppression of the host immune system resulting in various pathological diseases including lung cancer growth and metastasis. Thus, an investigation of potent immune mediator(s) involved in mediating UVB/CS-induced immunosuppression could lead to an identification of novel strategies to block these deleterious effects. Our previous studies have shown that novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate UVB/CS induced systemic immunosuppression. In addition, these UVB-generated oxidized-PAF-R-agonists augment experimental murine B16F10 melanoma tumor growth in a PAF-R-dependent manner mediated via upregulation of suppressive immune cell types, regulatory T cells (Tregs). As CS generates PAF-R agonists, our recently published studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we have demonstrated that treatment of syngeneic C57BL/6 mice with a PAF-R agonist augments lung tumor growth and its metastasis to the lung in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was observed to be dependent on host rather than tumor cells PAF-R as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

How did you come to be involved in your area of study?

Our previous studies have provided compelling evidences that oxidized PAF-R agonists produced via pro-oxidative stressors such as UVB induce systemic immunosuppression in a PAF-R dependent manner. However, the functional significance of this PAF-R agonists mediated systemic immunosuppressive effects was not known. We have recently shown that chronic persistence of host immunosuppression results in enhanced growth of murine B16F10 melanoma tumors. However, whether this PAF-R agonists mediated effects are limited to melanoma or is a generalized event and could also affect the growth of other tumor types was unknown. In our recently published article, we sought to determine if PAF-R agonists induced systemic immunosuppression could modulate the growth of lung cancer and its metastasis using murine LLC1 lung cancer cells as a model. This published study has significant relevance as we have shown that exposure to cigarette smoke generates oxidized PAF-R agonists that mediates its systemic immunosuppressive effects.

What was previously known about the topic of your article?

Our previous studies have established that oxidized lipid mediators with PAF-R agonistic activity mediate the immunosuppressive effects of pro-oxidative stressor such as UVB that results in an augmentation of experimental murine B16F10 melanoma tumor growth in a PAF-R dependent manner.

How has your work in this area advanced understanding of the topic?

Exposure to cigarette smoke (active and passive) has been shown to exert immunosuppressive effects that result in various health-related issues including initiation and progression of lung cancer. However, the molecular mechanism involved in mediating this CS-induced systemic immunosuppression is not known. Our studies have provided a potential mechanism that PAF-agonists play critical role as effectors in CS-mediated immunosuppression that in a long run results in the progression of pre-existing lung tumors.

What do you regard as being the most important aspect of the results reported in the article?

These findings indicate that experimental lung cancer progression can be modulated by the PAF-R signaling.

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