Many Roles of CCL20: Emphasis on Breast Cancer

Osuala, Kingsley; Sloane, Bonnie F.

doi:10.14304/surya.jpr.v2n3.2

Cited by 13 publications

(17 citation statements)

References 107 publications

(108 reference statements)

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“…As mentioned previously, ELISA analysis of M2a macrophage conditioned cell medium revealed lower levels of CCL-20 and CXCL-9 vs. M2b or M2c conditioned medias. Therefore, we tested whether CCL-20 or CXCL-9 had an inhibitory effect on M2a-induced migratory responses, as some contradiction in the literature exists as to the role of each of these cytokines (35, 36). Stimulation of either MDA-231 cells or SUM-149 cells with recombinant CXCL9 (rCXCL9; 50 ng/mL), recombinant CCL-20 (rCCL-20; 50 ng/mL), or a combination of both cytokines each had no inhibitory effect on M2a-mediated migration in a wound closure assay (Supplementary Figure S4).…”

Section: Resultsmentioning

confidence: 99%

IL-4/IL-13 Stimulated Macrophages Enhance Breast Cancer Invasion Via Rho-GTPase Regulation of Synergistic VEGF/CCL-18 Signaling

Little

Pathanjeli

et al. 2019

Front. Oncol.

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Tumor associated macrophages (TAMs) are increasingly recognized as major contributors to the metastatic progression of breast cancer and enriched levels of TAMs often correlate with poor prognosis. Despite our current advances it remains unclear which subset of M2-like macrophages have the highest capacity to enhance the metastatic program and which mechanisms regulate this process. Effective targeting of macrophages that aid cancer progression requires knowledge of the specific mechanisms underlying their pro-metastatic actions, as to avoid the anticipated toxicities from generalized targeting of macrophages. To this end, we set out to understand the relationship between the regulation of tumor secretions by Rho-GTPases, which were previously demonstrated to affect them, macrophage differentiation, and the converse influence of macrophages on cancer cell phenotype. Our data show that IL-4/IL-13 in vitro differentiated M2a macrophages significantly increase migratory and invasive potential of breast cancer cells at a greater rate than M2b or M2c macrophages. Our previous work demonstrated that the Rho-GTPases are potent regulators of macrophage-induced migratory responses; therefore, we examined M2a-mediated responses in RhoA or RhoC knockout breast cancer cell models. We find that both RhoA and RhoC regulate migration and invasion in MDA-MB-231 and SUM-149 cells following stimulation with M2a conditioned media. Secretome analysis of M2a conditioned media reveals high levels of vascular endothelial growth factor (VEGF) and chemokine (C-C motif) ligand 18 (CCL-18). Results from our functional assays reveal that M2a TAMs synergistically utilize VEGF and CCL-18 to promote migratory and invasive responses. Lastly, we show that pretreatment with ROCK inhibitors Y-276332 or GSK42986A attenuated VEGF/CCL-18 and M2a-induced migration and invasion. These results support Rho-GTPase signaling regulates downstream responses induced by TAMs, offering a novel approach for the prevention of breast cancer metastasis by anti-RhoA/C therapies.

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Section: Resultsmentioning

confidence: 99%

IL-4/IL-13 Stimulated Macrophages Enhance Breast Cancer Invasion Via Rho-GTPase Regulation of Synergistic VEGF/CCL-18 Signaling

Little

Pathanjeli

et al. 2019

Front. Oncol.

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“…The ligand for CCR6, CCL20 was higher in ductal and medullary breast carcinoma when compared to normal controls and other histological tissue types. Moreover, BrCa cells secrete CCL20, which recruits CCR6 expressing immune cells in the tumor vicinity 60 . Tumor cell produced CCL20/MIP3α allows them to attract CCR6 positive dendritic cell precursors 61 .…”

Section: Discussionmentioning

confidence: 99%

CC chemokines are differentially expressed in Breast Cancer and are associated with disparity in overall survival

Thomas

Mir

Kapur

et al. 2019

Sci Rep

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Despite recent advances, breast cancer (BrCa) still affects many women and the impact is disproportional in African Americans (AA) compared to European Americans (EA). Addressing socioeconomic and behavioral status has not been enough to reduce disparity, suggesting contribution of biological differences in BrCa disparity. Our laboratory was first to show involvement of CC chemokines in BrCa. In this study, using ONCOMINE, TCGA, bc-GenExMiner and KMplotter, we examined the association of CC chemokines in BrCa outcomes and disparity. We show over-expression of CCL5, -7, -11, -17, -20, -22 and -25 in BrCa tissues. High mRNA levels of CCL7, -8, -17, -20 and -25 predicted a decrease in overall survival (OS). CCL7 and CCL8 were associated with decreased relapse-free survival. Expression of CCL17 and CCL25 was associated with decreased OS in AA. In EA, CCL8 was associated with decreased OS. Expression of CCL5, -7, -8, -17, -20 and -25 was highest in TNBC. Expression of CCL11 and CCL22 was associated with HER2. CCL7, -8, -17, -20 and -25 were elevated in AAs. In conclusion, our analysis suggests significant association of CC-chemokines in BrCa progression, OS and disparate disease outcome in AA compared to EA patients.

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“…This correlation was also observed in our study, which indicates a similar role in BC (Table ; Liu et al ., ). In contrast to CCL4, CCL20 has been shown to have several important functions in BC (Osuala and Sloane, , p. 20).…”

Section: Discussionmentioning

confidence: 99%

Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer

et al. 2019

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There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow‐up of personalized cancer therapy, including immunotherapy. Fine‐needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL‐6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune‐related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.

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Many Roles of CCL20: Emphasis on Breast Cancer

Cited by 13 publications

References 107 publications

IL-4/IL-13 Stimulated Macrophages Enhance Breast Cancer Invasion Via Rho-GTPase Regulation of Synergistic VEGF/CCL-18 Signaling

IL-4/IL-13 Stimulated Macrophages Enhance Breast Cancer Invasion Via Rho-GTPase Regulation of Synergistic VEGF/CCL-18 Signaling

CC chemokines are differentially expressed in Breast Cancer and are associated with disparity in overall survival

Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer

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