What does this research mean for the field?

Transglutaminase 2 (TG2) promotes distant hematogenous metastasis and tumor aggressiveness in breast cancer by driving interleukin-6 (IL-6) production. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to explore the influence of transglutaminase 2 (TG2) and interleukin-6 (IL-6) on breast cancer metastasis and aggressiveness.

October 3, 2011Open Access

Transglutaminase 2 facilitates the distant hematogenous metastasis of breast cancer by modulating interleukin-6 in cancer cells

KOKeunhee OhSillaJen (South Korea)EKEunyoung KoStanford University HKHee Sung KimUlsan College

Key Points

This research aims to explore the influence of transglutaminase 2 (TG2) and interleukin-6 (IL-6) on breast cancer metastasis and aggressiveness.
Generated TG2 and IL-6-knocked-down breast cancer cells using shRNA.
Utilized a human breast cancer xenograft model and tissue microarrays from 412 patients for analysis.
Analyzed associations between TG2 expression and clinical outcomes including recurrence-free and metastasis-free survival.
TG2 expression levels directly impacted IL-6 production in breast cancer cells.
Higher TG2 and IL-6 levels correlated with decreased distant metastasis-free survival (DMFS) in patients (P=0.006).
Combined high expression of TG2 and IL-6 indicated shorter DMFS compared to high IL-6 only (P=0.013).

Abstract

Abstract Introduction Inflammation has been implicated in cancer aggressiveness. As transglutaminase 2 (TG2), which has been associated with inflammatory signaling, has been suggested to play a role in tumor behavior, we propose that TG2 may be an important linker inducing interleukin (IL)-6-mediated cancer-cell aggressiveness, including distant hematogenous metastasis. Methods To investigate the role for TG2 and IL-6, TG2-knocked-down and IL-6-knocked-down cancer cells were generated by using shRNA. Human breast cancer cell xenograft model in highly immunocompromised mice and human advanced breast cancer primary tumor tissue microarrays were used in this study. Results IL-6 production in human breast cancer cells was dependent on their TG2 expression level. In vitro tumor-sphere formation was dependent on TG2 and downstream IL-6 production from cancer cells. Primary tumor growth in the mammary fat pads and distant hematogenous metastasis into the lung was also dependent on TG2 and downstream IL-6 expression levels. The effect of TG2 expression on human breast cancer distant metastasis was investigated by analyzing a tissue microarray of primary tumors from 412 patients with their clinical data after 7 years. TG2 expression in primary tumor tissue was inversely correlated with recurrence-free survival ( P = 0.019) and distant metastasis-free survival (DMFS) ( P = 0.006) in patients with advanced breast cancer. Furthermore, by using public datasets that included a total of 684 breast cancer patients, we found that the combined high expression of TG2 and IL-6 was associated with shorter DMFS, compared with the high expression of IL-6 only ( P = 0.013). Conclusions We provide evidence that TG2 is an important link in IL-6-mediated tumor aggressiveness, and that TG2 could be an important mediator of distant metastasis, both in a xenograft animal model and in patients with advanced breast cancer.

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Cite This Study

Oh et al. (Mon,) studied this question.

synapsesocial.com/papers/6a0d394b48a82a5ce309aaaa https://doi.org/https://doi.org/10.1186/bcr3034

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