Interleukin‐8 modulates growth and invasiveness of estrogen receptor‐negative breast cancer cells

Abstract

Breast cancer, especially estrogen receptor (ER)‐negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER‐negative breast cancers express high levels of interleukin‐8 (IL‐8), whereas their ER‐positive counterparts do not. IL‐8 is a multi‐functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL‐8 in ER‐negative breast cancer progression by using RNA interference to specifically knockdown IL‐8 expression in ER‐negative breast cancer cell lines MDA‐MB‐231 and MDA‐MB‐468. In vitro, suppression of IL‐8 led to significant reductions in cell invasion (p < 0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL‐8 significantly reduced the microvessel density (p < 0.05), and markedly reduced neutrophil infiltration into the tumors (p < 0.05). In contrast to in vitro observations, suppression of IL‐8 promoted tumor growth in nude mice (p < 0.05). Our results imply that the complex roles of IL‐8 in the regulation of ER‐negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL‐8. © 2007 Wiley‐Liss, Inc.

The CXCR2 Antagonist, SCH-527123, Shows Antitumor Activity and Sensitizes Cells to Oxaliplatin in Preclinical Colon Cancer Models

“…The role of IL-8 and CXCR2 in tumor development and progression has been well documented in a wide range of cancer types (8,(27)(28)(29)(30)(31). Our previous data and others have shown that the IL-8/CXCR2 pathway plays a key role in mediating colorectal cancer development (11,14,15,32).…”

Plasma interleukin-8 levels are persistently elevated for 1�month after minimally invasive colorectal resection for colorectal cancer

“…Various types of cancer including colon have been shown to express IL-8 (CXCR8) and its receptors CXCR1 and CXCR2 (23)(24)(25). Although IL-8 levels have been shown to be elevated in colorectal cancer patients, the tumor, once removed, cannot account for the postoperative elevation.…”

“…It is possible that the growth of residual tumor deposits may be stimulated since IL-8 has been shown to promote tumor growth in numerous experimental studies (19,20,23). It is also possible that IL-8, via different mechanisms, may encourage tumor angiogenesis (18,19).…”

“…IL-8 blockade has been demonstrated to inhibit tumor growth (22). IL-8 also plays a role in and is a marker of tumor progression and metastatic disease for a wide range of cancers including gliomas as well as breast and prostate cancers (23)(24)(25). Finally, IL-8 is prominent in keratinocytes after IHC staining; this presence suggests that it is a cell migration and chemotactic factor for keratinocytes, suggesting that IL-8 plays a role in wound healing (26,27).…”

A new perspective on Estrogen Receptor beta in breast cancer progression

“…23 Thus, IL-8 expression contributes to unfavorable outcomes, especially in ERα negative breast cancers. 24,25 Some studies demonstrated that HER2/neu breast cancers have elevated IL-8 expression and showed a correlation between HER2 and ERβ expression. 26,27 Based on these findings, the authors proposed the existence of a possible HER2/ERβ/IL-8 expression axis.…”