Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: A basis for tumor-promoting interactions

Soria, Gali; Yaal-Hahoshen, Neora; Azenshtein, Elina; Shina, Sima; Leider-Trejo, Leonor; Ryvo, Larisa; Cohen-Hillel, Efrat; Shtabsky, Alexander; Ehrlich, Marcelo; Meshel, Tsipi; Keydar, Iafa; Ben‐Baruch, Adit

doi:10.1016/j.cyto.2008.08.002

Cited by 80 publications

(57 citation statements)

References 55 publications

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“…Conversely, the combinations of CCL5-negative/ER-a-positive and CCL5-negative/PR-positive in the stage II group as a whole were strongly correlative with an improved prognosis. 33 Furthermore, concomitant expression of the CCL5 and MCP-1 was observed in advanced human BC, 34 suggesting tumor-promoting interactions between these two chemokines. By immunohistochemistry analysis for the expression of CCL2, CCL5, IL-1b and TNF-a, Soria et al examined four groups of patients diagnosed with (i) benign breast disorders; (ii) ductal carcinoma in situ; (iii) invasive ducal carcinoma (IDC) without relapse; and (iv) IDC with relapse, respectively.…”

Section: Ccl5 and Human Breast Cancer (Bc)mentioning

confidence: 99%

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

Zhang

Kim

et al. 2013

Cell Mol Immunol

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Breast cancer (BC) is a leading cause of mortality among women in the world. To date, a number of molecules have been established as disease status indicators and therapeutic targets. The best known among them are estrogen receptor-a (ER-a), progesterone receptor (PR) and HER-2/neu. About 15%-20% BC patients do not respond effectively to therapies targeting these classes of tumor-promoting factors. Thus, additional targets are strongly and urgently sought after in therapy for human BCs negative for ER, PR and HER-2, the so-called triple-negative BC (TNBC). Recent clinical work has revealed that CC chemokine ligand 5 (CCL5) is strongly associated with the progression of BC, particularly TNBC. How CCL5 contributes to the development of TNBC is not well understood. Experimental animal studies have begun to address the mechanistic issue. In this article, we will review the clinical and laboratory work in this area that has led to our own hypothesis that targeting CCL5 in TNBCs will have favorable therapeutic outcomes with minimal adverse impact on the general physiology.

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Section: Ccl5 and Human Breast Cancer (Bc)mentioning

confidence: 99%

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

Zhang

Kim

et al. 2013

Cell Mol Immunol

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“…In terms of breast cancer, a number of studies have suggested that RANTES is associated with breast malignancy. In patients with breast cancer, advanced disease, early relapse, and poor prognosis are significantly correlated with elevated RANTES expression levels in biopsy specimens and serum (26)(27)(28). Therefore, the precise role of RANTES signaling in breast cancer should be clarified.…”

Section: Introductionmentioning

confidence: 99%

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

Lee

et al. 2013

Molecular Cancer Research

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The acquisition of tamoxifen resistance is a major therapeutic problem in breast cancer. We developed a tamoxifen-resistant MCF-7 (TRM-7) cell line to elucidate the molecular mechanisms and factors associated with acquisition of such resistance. We showed that phosphorylation of STAT3 at tyrosine 705 (Y705) and RANTES expression are increased in response to tamoxifen in human breast cancer cells. On the basis of these results, we hypothesize that upregulated STAT3 phosphorylation and RANTES may be correlated with the development of drug resistance. Here, we showed that STAT3 and RANTES contribute to the maintenance of drug resistance. STAT3 phosphorylation is constitutively retained via a RANTES autocrine loop, which in turn upregulates antiapoptotic signals in TRM-7 cells. STAT3-RANTES autocrine signaling affected expression of anti-apoptotic BCL-2 family genes and prevented TRM-7 cells from undergoing programmed cell death by inhibiting PARP and caspase-9 cleavage. Subsequently, blockade of STAT3 and RANTES in TRM-7 cells resulted in reduction of antiapoptotic signals, which was rescued by exogenous RANTES treatment; drug resistance was also restored. Taken together, our results suggested that STAT3-RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death. These mechanisms of STAT3-RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors. Mol Cancer Res; 11(1); 31-42. Ó2012 AACR. IntroductionBreast cancer is the second most common cancer worldwide after lung cancer, the fifth most common cause of cancer death, and the leading cause of cancer death in women. The global burden of breast cancer exceeds that of all other cancers, and its incidence is increasing (1). In women younger than 50 years with breast cancer, chemotherapy increases the 15-year survival rate by 10%,

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“…MCP-1 is expressed at relatively low levels in normal mammary epithelial tissue and circulating plasma, but increases dramatically with breast cancer progression. 13,[33][34][35] Recently, MCP-1 has been shown to signal to breast cancer cells to regulate survival and invasion, 14 promote primary tumor growth, 15 and mediate breast cancer metastasis. 36 Interestingly, TNBC educated macrophages secrete higher amounts of MCP-1 than macrophages co-cultered with estrogen receptor positive breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

Cranford

Velázquez

Enos

et al. 2017

Cancer Biology & Therapy

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Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC. Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes. Histopathological scoring was performed at 12 weeks of age and 23 weeks of age. Gene expression of macrophage markers and inflammatory mediators were measured in the mammary gland and tumor microenvironment at sacrifice. As expected, MCP-1 depletion resulted in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression represented by histopathological scoring (12 weeks of age). Deficiency in MCP-1 significantly downregulated expression of macrophage markers in the mammary gland (Mertk and CD64) and the tumor microenvironment (CD64), and also reduced expression of inflammatory cytokines in the mammary gland (TNFa and IL-1b) and the tumor microenvironment (IL-6). These data support the hypothesis that MCP-1 expression contributes to increased tumorigenesis in a model of TNBC via recruitment of macrophages and subsequent increase in inflammatory mediators.

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Concomitant expression of the chemokines RANTES and MCP-1 in human breast cancer: A basis for tumor-promoting interactions

Cited by 80 publications

References 55 publications

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

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