To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

Geng, Bin; Zhao, Wenying

doi:10.1002/eji.201343875

Cited by 10 publications

(7 citation statements)

References 7 publications

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“…Our data demonstrate that IL‐22 + and IL‐17 + T cells are enriched in the tumor microenvironment of BCCs and SCCs. Our result is consistent with studies that indicate the elevated IL‐17 and IL‐22 expression in several human tumors, such as ovarian cancer, prostate cancer, breast cancer, hepatocellular carcinoma, esophageal cancer, and gastric cancer .…”

Section: Discussionsupporting

confidence: 93%

Interleukin‐17 and interleukin‐22 promote tumor progression in human nonmelanoma skin cancer

et al. 2015

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Interleukin-17 (IL-17Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNonmelanoma skin cancer (NMSC) represents one of the most common malignancies in humans and keratinocyte-derived basalcell carcinomas (BCCs) and squamous-cell carcinomas (SCCs) are responsible approximately for the 80 and 20% NMSC cases, respectively [1,2]. Both types of NMSCs share important risk factors, such as fair skin and high degree of sun exposure [3]. Nevertheless, BCCs and SCCs have distinct metastatic attitude, being rare in BCC and much more common in SCC [4].Correspondence: Dr. Andrea Cavani e-mail: cavani@idi.itTumor-infiltrating lymphocytes (TILs) are frequently found in malignant tumors, being suggestive of a host antitumoral immune response. Several independent studies have demonstrated that the presence of TILs correlated with increased survival and represents a predictive as well as prognostic biomarker in patients with breast cancer, colorectal cancer, glioma, and gastric cancer [5][6][7]. However, dissimilar data revealed that TILs functionally promoted epithelial carcinogenesis [8], and that TIL-secreted chemokines contributed to tumor angiogenesis and growth [9]. Although few studies have described the inflammatory infiltrate of BCCs and Table 1), but not that of the Th1-cell clone 6.1, was able to induce proliferation of both M77015 ( Fig. 2D and E) and CAL27 cells (Fig. 2F and G). To demonstrate that tumor-cell growth induced by supernatant of activated TIL-derived cell clones was dependent on IL-17 and IL-22, we performed blocking experiments with anti-IL-17 and anti-IL-22 Abs. As shown in Figure 2, results clearly indicate the capacity of both IL-17 and IL-22 blocking antibodies to reduce M77015 and CAL27 proliferation induced by supernatant of TILderived cell clones ( Fig. 2D-G). Furthermore, IL-17 and IL-22 were able to induce CAL27-and M7715-cell migration in an in vitro scratch assay (Fig. 3), indicating that the cytokines promote local invasiveness of tumor cells. IL-6 and IL-8 are induced in SCC cells by IL-17 treatmentThe next step was to investigate whether IL-17 and IL-22 alone or in combination with other Th17-and/or Th22-derived cytokines could induce the secretion of cytokines and/or chemokines, known to influence tumor survival and progression, in tumor cells. Indeed, our previous data showed that in normal human keratinocytes [28,29], IL-17, alone or in combination with TNF-α, induced the secretion of IL-8. To verify whether IL-17 had similar effects on BCC-and SCC-cell lines, we exposed CAL27 and M77015 cells to recombinant human IL-17, IL-22, with or without TNF-α, and cytokine release was investigated by ELISA. In particular, we decided to analyze IL-6 and IL-8 release, as it is known that both cytokines induce proliferation and invasion of many tumor cells [30][31][32]. As shown in Figure 4, IL-17, but not IL-22 alone, augmented both IL-6 ( Fig. 4A) and IL-8 ( Fig. 4B) secretion by CAL27 cells. Moreover, IL-17 showed a s...

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Section: Discussionsupporting

confidence: 93%

Interleukin‐17 and interleukin‐22 promote tumor progression in human nonmelanoma skin cancer

et al. 2015

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“…IL-17 is also a growth factor for PCa cells 50 and has a role in bone metastasis from BCa. 51 Immune cells can also produce factors that stimulate angiogenesis and prepare the pre-metastatic niche for bone metastasis and serve as OCL precursors. Mesenchymal stromal cells produce large amounts of IL-6 that enhances the growth and prevents apoptosis of myeloma cells, and stimulates OCL formation, as well as produce RANK ligand.…”

Section: Role Of Immune Cells In Bone Metastasismentioning

confidence: 99%

Mechanisms of osteolytic and osteoblastic skeletal lesions

Roodman

Silbermann

2015

BoneKEy Reports

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The bone is a frequent site for tumor metastasis, and cancer in the bone results in marked disturbances of bone remodeling that can be lytic, blastic or a combination of the two. Patients with advanced malignancies that have metastasized to the bone frequently suffer from debilitating skeletal-related events, including pathologic fractures, spinal cord compression syndromes, disorders of calcium and phosphate homeostasis and severe cancer-related pain. This review will discuss recent studies on the mechanisms responsible for osteolytic and osteoblastic metastasis and how their identification has resulted in the development of new agents for patients with metastatic bone disease.

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“…Tumor infiltrating Th17 cells and IL-17 induced the expression of granulocyte-colony stimulating factor (G-CSF) leading to immature myeloid cell recruitment into the tumor microenvironment and anti-VEGF therapy resistance through the production of proangiogenic Bv8 by these myeloid cells [ 31 ]. In patients with invasive ductal carcinoma (IDC), tumor aggressiveness was reported to be enhanced by IL-17 via induction of angiogenic factors, such as chemokine CXCL8, MMP-2, MMP-9, and VEGF [ 16 , 32 ]. Similarly, injection of recombinant IL-17 in the murine breast cancer model 4T1 was shown to increase microvascular density, a parameter for tumor angiogenesis [ 33 ].…”

Section: Role Of Il-17 In Breast Cancermentioning

confidence: 99%

Interleukin‐17 Could Promote Breast Cancer Progression at Several Stages of the Disease

Welte

Zhang

2015

Mediators of Inflammation

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Metastatic disease accounts for more than 90% of deaths from breast cancer. Yet the factors that trigger metastasis, often years after primary tumor removal, are not understood well. Recently the proinflammatory cytokine interleukin- (IL-) 17 family has been associated with poor prognosis in breast cancer. Here we review current literature on the pathogenic mechanisms driven by IL-17 during breast cancer progression and connect these findings to metastasis. These include (1) direct effects of IL-17 on tumor cells promoting tumor cell survival and invasiveness, (2) regulation of tumor angiogenesis, and (3) interaction with myeloid derived suppressor cells (MDSCs) to inhibit antitumor immune response and collaborate at the distant metastatic site. Furthermore, IL-17 might also be a culprit in bone destruction caused by late stage bone metastasis. Interestingly, in addition to these potential prometastasis functions, there is also evidence for an opposite, antitumor role of IL-17 during cancer therapies. We hypothesize that these contradictory roles may be due to chronic, imbalanced versus acute transient nature of the immune reactions, as well as differences in the cells that interact with IL-17+ cells under different circumstances.

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To the Editor IL‐17, an important prognostic factor and potential therapeutic target for breast cancer?

Cited by 10 publications

References 7 publications

Interleukin‐17 and interleukin‐22 promote tumor progression in human nonmelanoma skin cancer

Interleukin‐17 and interleukin‐22 promote tumor progression in human nonmelanoma skin cancer

Mechanisms of osteolytic and osteoblastic skeletal lesions

Interleukin‐17 Could Promote Breast Cancer Progression at Several Stages of the Disease

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