Assessment of chemokine serum levels in epithelial ovarian cancer patients

Falcão-Júnior, João Oscar Almeida; Teixeira-Carvalho, Andréa; Cândido, Eduardo Batista; Lages, Elisa Lopes e; Guevara‐Balcazar, Gustavo; Lamaita, Rívia Mara; Bonfim, Lívia Paula Freire; Salera, Rafael Borges; Paulo, p.; Silva-Filho, Agnaldo L.

doi:10.1177/030089161309900417

Cited by 7 publications

(7 citation statements)

References 16 publications

(25 reference statements)

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“…Ding et al [24] noted significantly lower MCP-1 and CCL3 serum concentrations in patients with oral squamous cell carcinoma and leukoplakia. Similar results were obtained for ovarian and colorectal cancer [25–27]. Tsaur et al [28] reported down-regulation of MCP-1 and gene expression of other chemokines in renal cell cancer.…”

Section: Discussionsupporting

confidence: 76%

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

Sobjanek¹,

Zabłotna²,

Szczerkowska-Dobosz³

et al. 2016

pdia

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IntroductionPolymorphic variants of MCP-1 and RANTES genes and their protein serum levels have been implicated in the increased risk and severity of several malignancies. However, the subject has not been explored in basal cell carcinoma (BCC) patients so far.AimTo investigate the association between monocyte chemoattractant protein 1 (MCP-1) (–2518 A/G) and RANTES (–403 G/A) polymorphism and risk and clinical course of BCC.Material and methodsThe study group consisted of 150 unrelated patients with BCC and 140 healthy, unrelated, age- and sex-matched volunteers. The polymorphisms were analysed using the amplification refractory mutation system polymerase chain reaction method (ARMS-PCR) and single specific primer-polymerase chain reaction (SSP-PCR). Serum cytokine levels were measured with ELISA.ResultsThe presence of the MCP-1 –2518 GG genotype was statistically more frequent in BCC patients and it increased the risk of BCC (OR = 2.63, p = 0.003). Genotype –330 GG was statistically more common in patients with less advanced tumours (OR = 2.8, p = 0.017). Monocyte chemoattractant protein 1 serum level was statistically higher with GG genotype. In the BCC group MCP-1 serum levels were decreased. Neither polymorphic variants of RANTES nor the chemokine serum concentration differed significantly between the study groups.ConclusionsThese findings suggest that –2518 A/G MCP-1 polymorphism may be involved in BCC pathogenesis.

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Section: Discussionsupporting

confidence: 76%

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

Sobjanek¹,

Zabłotna²,

Szczerkowska-Dobosz³

et al. 2016

pdia

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“…Compared to healthy controls, both lower levels 28,29 as higher levels of CCL-2 30,31 are reported. Some studies claim that higher levels are associated with advanced disease.…”

Section: Discussionmentioning

confidence: 91%

“…Acts immune suppressive, increases proteolytic activity of cells, adhesion and directly stimulates angiogenesis 44 Inhibits the function of CD8 C cytotoxic T cells and Th1 cells Inhibits the development of M1 macrophages from monocytes and plays an indispensable role in tumor development and progression 45 TGFß1 mRNA expression is an indicator of tumor sensitivity to standard therapy that it can identify biologically aggressive and highly malignant tumors and can predict the prognosis of patients with ovarian cancer 46 Serum level of TGF-b1 has no diagnostic and prognostic role and is associated with sensitivity to standard chemotherapy in ovarian cancer patients 47 CCL-2 /MCP-1 One of the key chemokines that regulate migration and infiltration of monocytes, memory T cells, NKC and DC to sites of inflammation. Has both tumor growth-promoting as growth-inhibiting influences 48,49 Chemotherapy (paclitaxel-carboplatin) can upregulate CCL-2 expression 50 Elevated CCL-2 expression by ovarian cancer cells is reported to be associated both with a better chemotherapy (paclitaxelcisplatin) responses 51 as with chemotherapy resistance 52 CCL-2 levels in serum of ovarian cancer patients compared to healthy controls are both described to be lower 28,29 as higher 30,31 Higher levels are associated with advanced disease 30,31 …”

Section: Tgf-bmentioning

confidence: 99%

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

et al. 2015

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Neoplastic cells can escape immune control leading to cancer growth. Regulatory T cells (Treg), myeloidderived suppressor cells (MDSC) and tumor-associated macrophages (TAM) are crucial in immune escape. TAM are divided based on their immune profile, M1 are immunostimulatory while M2 are immunosuppressive. Research so far has mainly focused on the intratumoral behavior of these cells. This study, on the other hand, explored the systemic changes of the key metabolites [IL-4 (interleukin), IL-13, arginase, IL-10, VEGF-A (vascular endothelial growth factor), CCL-2 (chemokine (C-C) motif ligand 2) and TGF-b (transforming growth factor)] linked to Treg, MDSC and TAM during the course of the disease in ovarian and fallopian tube cancer patients. Serum samples were therefore analyzed at diagnosis, after (interval)-debulking surgery and after chemotherapy (paclitaxel-carboplatin). We also determined galectin-1 (gal-1), involved in angiogenesis and tumor-mediated immune evasion. We found significantly lower levels of IL-10, VEGF-A, TGF-b and arginase and higher levels of gal-1 after chemotherapy compared to diagnosis. After debulking surgery, a decrease in IL-10 was significant. Gal-1 and CCL-2 appeared independent prognostic factors for progression-free and overall survival (OS) (multivariate analysis). These results will help us in the decision making of future therapies in order to further modulate the immune system in a positive way.

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“…These results indicated that MIP-1β was necessary and sufficient for the observed increase in tumor adhesion, but an analysis of the current literature did not indicate a clear role for MIP-1β in HGSOC. For example, the concentration of MIP-1β in serum was reported to be lower in HGSOC patients compared to benign patients (38). However, matched ascites and serum samples from HGSOC patients indicated that the concentration of MIP-1β was higher in ascites compared to serum levels (33) suggesting that MIP-1β is concentrated in the peritoneal microenvironment of HGSOC patients.…”

Section: Discussionmentioning

confidence: 99%

“…(B) LP-9 were treated with 10% (v/v) of PBS (Veh) or ascites in SFM in conjunction with an isotype control or MIP-1β blocking antibody for 24 hours, n=3 for each patient sample with OV90 cell line. (C) The Kaplan-Meier plotter tool (38) was utilized with Gene Omnibus and The Cancer Genome Atlas databases to calculate PFS for HGSOC patients with low and high expression of CD24 . (D) Representative omental tissue sections from patients with non-HGSOC or HGSOC conditions stained for P-selectin and calretinin (mesothelial cells).…”

Section: Figurementioning

confidence: 99%

Alternatively-Activated Macrophages Upregulate Mesothelial Expression of P-Selectin to Enhance Adhesion of Ovarian Cancer Cells

et al. 2018

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Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a coculture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAM) influence the adhesion of tumor cells to mesothelial cells. We found that AAM-secreted MIP-1β activates CCR5/PI3K signaling in mesothelial cells, resulting in expression of P-selectin on the mesothelial cell surface. Tumor cells attached to this P-selectin through CD24, resulting in increased tumor cell adhesion in static conditions and rolling underflow. C57/BL6 mice treated with MIP-1β exhibited increased P-selectin expression on mesothelial cells lining peritoneal tissues, which enhanced CaOV3 adhesion and ID8 adhesion Analysis of samples from patients with HGSOC confirmed increased MIP-1β and P-selectin, suggesting that this novel multicellular mechanism could be targeted to slow or stop metastasis in HGSOC by repurposing anti-CCR5 and P-selectin therapies developed for other indications. This study reports novel insights on the peritoneal dissemination occurring during progression of ovarian cancer and has potential for therapeutic intervention. http://cancerres.aacrjournals.org/content/canres/78/13/3560/F1.large.jpg .

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Assessment of chemokine serum levels in epithelial ovarian cancer patients

Cited by 7 publications

References 16 publications

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

–2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

Immunosuppressive parameters in serum of ovarian cancer patients change during the disease course

Alternatively-Activated Macrophages Upregulate Mesothelial Expression of P-Selectin to Enhance Adhesion of Ovarian Cancer Cells

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