Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer

Wolf, Ronald; Voscopoulos, Christopher; Winston, Jason; Dharamsi, Alif; Goldsmith, Paul K.; Gunsior, Michele; Vonderhaar, Barbara K.; Olson, Melanie; Watson, Peter H.; Yuspa, Stuart H.

doi:10.1016/j.canlet.2008.11.032

Cited by 33 publications

(44 citation statements)

References 16 publications

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“…On the other hand, the lack of a significant association between any S100 transcript and lymph node metastasis suggests that these genes are unlikely to be involved in local metastasis to lymph nodes. Consistent with our findings, Wolf et al [15] previously reported that S100A7 was upregulated in steroid receptornegative compared to steroid receptor-positive breast cancer. These authors also found that S100A15 was increased in receptor negative vis-à-vis receptor positive samples.…”

Section: Discussionsupporting

confidence: 95%

The role of S100 genes in breast cancer progression

et al. 2010

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The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.

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Section: Discussionsupporting

confidence: 95%

The role of S100 genes in breast cancer progression

et al. 2010

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“…Previously, it has been shown that hS100A7 modulates VEGF expression in MDA-MB-468 cells (7). These studies suggest hS100A7 which has been shown to be associated with highly-invasive breast cancer subtypes (31) may enhance metastasis through enhancement of pro-metastatic and angiogenic molecules.…”

Section: Discussionmentioning

confidence: 87%

“…mS100a7a15 has also been shown to be associated with inflammation (31). Similar to hS100A7, mS100a7a15 overexpression in two different clones of MDA-MB-231 (M1 and M2) enhanced proliferation (Fig.…”

Section: Resultsmentioning

confidence: 99%

S100A7 Enhances Mammary Tumorigenesis through Upregulation of Inflammatory Pathways

et al. 2012

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S100A7/Psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive ER-negative (ERα-) breast cancers. However, it has not been established whether S100A7 contributes to breast cancer growth or metastasis. Here, we report the consequences of its expression on inflammatory pathways that impact breast cancer growth. Overexpression of human S100A7 or its murine homolog mS100a7a15, enhanced cell proliferation and upregulated various pro-inflammatory molecules in ERα- breast cancer cells. To examine in vivo effects, we generated mice with an inducible form of mS100a7a15 (MMTV-mS100a7a15 mice). Orthotopic implantation of MVT-1 breast tumor cells into the mammary glands of these mice enhanced tumor growth and metastasis. Compared to uninduced transgenic control mice, the mammary glands of mice where mS100a7a15 was induced exhibited increased ductal hyperplasia and expression of molecules involved in proliferation, signaling, tissue remodeling and macrophage recruitment. Furthermore, tumors and lung tissues obtained from these mice showed further increases in pro-metastatic gene expression and recruitment of tumor-associated macrophages (TAMs). Notably, in vivo depletion of TAM inhibited the effects of mS100a7a15 induction on tumor growth and angiogenesis. Further, introduction of soluble hS100A7 or mS100a7a15 enhanced chemotaxis of macrophages via activation of RAGE receptors. In summary, our work employed a powerful new model system to demonstrate that S100A7 enhances breast tumor growth and metastasis by activating proinflammatory and metastatic pathways.

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“…Expression of IL-1β, caspase-1, caspase-5, NLRP1, NLRP3 and AIM2 was analyzed by SYBR Green supermix in CFX96-real-time detection system (Bio-Rad Laboratories, Hercules, CA, USA), calculated with the ΔC T method [28] and compared to housekeeping genes, β -actin or PBGD (Qiagen, Hilden, Germany). Results are shown as fold induction of healthy tissue or unstimulated conditions.…”

Section: Methodsmentioning

confidence: 99%

Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation

et al. 2017

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IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.

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Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer

Cited by 33 publications

References 16 publications

The role of S100 genes in breast cancer progression

The role of S100 genes in breast cancer progression

S100A7 Enhances Mammary Tumorigenesis through Upregulation of Inflammatory Pathways

Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation

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