Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer.
BACKGROUND
Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interleukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.


METHODS
Interfering pRNA-IL-8 and the control was transfected into ER (-) MDA-MB-231. The proliferation, cell apotosis, and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).


RESULTS
In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P < 0.001), but had no effect on cell proliferation (P > 0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P = 0.001, P < 0.001). Less metastasis was found in transfected cells compared with negatively transfected cells (0% vs 80%, P = 0.048). Nevertheless, we observed less MVD in transfected cells compared with control in nude mice (P < 0.001).


CONCLUSIONS
IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may be correlated with neutrophils infiltration induced by IL-8.
Yao
Chen
C
Division of Breast Surgery, Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Lin
Ying
Y
Ye
Cai-sheng
CS
Bi
Jiong
J
Zhu
Yi-fan
YF
Wang
Shen-ming
SM
D017209:Apoptosis; D001943:Breast Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020556:Neutrophil Infiltration; D034741:RNA, Small Interfering / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000032:analysis
D016209:Interleukin-8; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen