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The contrasting roles of inflammasomes in cancer.

ABSTRACT: Chronic inflammation plays a decisive role at different stages of cancer development. Inflammasomes are oligomeric protein complexes activated in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs and DAMPs are released from infected cells, tumors and damaged tissues. Inflammasomes activate and release inflammatory cytokines such as IL-1? and IL-18. The various inflammasomes and inflammatory cytokines and chemokines play contrasting roles in cancer development and progression. In this review, we describe the roles of different inflammasomes in lung, breast, gastric, liver, colon, and prostate cancers and in glioblastomas.

SUBMITTER: He Q

PROVIDER: S-EPMC5934549 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The contrasting roles of inflammasomes in cancer.

He Qin Q Fu Yu Y Tian Dean D Yan Wei W

American journal of cancer research 20180401 4

Chronic inflammation plays a decisive role at different stages of cancer development. Inflammasomes are oligomeric protein complexes activated in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs and DAMPs are released from infected cells, tumors and damaged tissues. Inflammasomes activate and release inflammatory cytokines such as IL-1β and IL-18. The various inflammasomes and inflammatory cytokines and chemokines play contrasting ...[more]

PMID: 29736304

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Project description:ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2 (P=0.01). Transport studies showed that wild-type ABCG2 was able to efflux more folic acid than the Q141K variant (P<0.002), suggesting that retained tumoral folate contributes to the decreased time to PSA recurrence in the Q141K variant patients. In a seemingly conflicting study, it was previously reported that docetaxel-treated Q141K variant prostate cancer patients have a longer survival time. We found this may be due to less efficient docetaxel efflux in cells with the Q141K variant versus wild-type ABCG2. In human prostate cancer tissues, confocal microscopy revealed that all genotypes had a mixture of cytoplasmic and plasma membrane staining, with noticeably less staining in the two homozygous KK patients. In conclusion, the Q141K variant plays contrasting roles in prostate cancer: 1) by decreasing folate efflux, increased intracellular folate levels result in enhanced tumor cell proliferation and therefore time to recurrence decreases; and 2) in patients treated with docetaxel, by decreasing its efflux, intratumoral docetaxel levels and tumor cell drug sensitivity increase and therefore patient survival time increases. Taken together, these data suggest that a patient's ABCG2 genotype may be important when determining a personalized treatment plan.

Dataset Information

The contrasting roles of inflammasomes in cancer.

Publications

The contrasting roles of inflammasomes in cancer.

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