Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones

详细信息    查看全文

• 作者：Awatef Ben Jemaa^a ; Yosra Bouraoui^a ; Nawfel Ben Rais^b ; Yassine Nouira^c ; Ridha Oueslati^a ; ^{oueslatiridha12@hotmail.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PSMA ; prostate specific membrane antigen ; PSA ; prostate specific antigen ; BPH ; benign prostate hyperplasia ; PC ; prostate cancer ; IL-6 ; interleukin-6 ; IL-1α ; interleukin-1α ; TNF-α ; tumor necrosis factor
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：221
• 期：12
• 页码：1424-1431
• 全文大小：1959 K

文摘

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear.

Aim

We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups.

Materials and methods

27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser.

Results

In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA−) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4–20 ng/mL or >20 ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα−) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA−) and (PSMA+,PSA+) BPH sub-groups.

Conclusion

Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones.