Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer

Santin, Alessandro D.; Bellone, Stefania; Ravaggi, Antonella; Román, Juan José Mora; Smith, Carl V.; Pecorelli, Sërgio; Cannon, Martin J.; Parham, Groesbeck P.

doi:10.1111/j.1471-0528.2001.00206.x

Cited by 41 publications

(31 citation statements)

References 44 publications

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“…Furthermore, TGF-β1 stimulates matrix metalloproteinase secretion, thereby promoting OC cell invasion [39]. Several clinical studies report that TGF-β1 and TGF-β1-binding protein mRNAs are elevated in OC tissue and in ascites fluid [19,40]. Although melatonin has been shown to activate the TGF-β1 pathway related to growth inhibition of breast cancer cells [41], we observed an antagonizing effect of melatonin on TGF-β1 and VEGF levels in the course of OC treatment.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Zonta

Martinez

Camargo

et al. 2017

IJMS

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Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Zonta

Martinez

Camargo

et al. 2017

IJMS

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“…Interestingly, the immunosuppressive cytokine TGF-β, which is regularly detected in ovarian and cervical cancer (45)(46)(47), seems to induce this inhibiting receptor on T cells (44). Several studies have shown that the inhibiting receptor CD94/NKG2A dampens the incoming activation signals of T cells by recruitment of phosphatases like SHP-1 to the signal transducing synaps, resulting in decreased effector functions (1,44,48).…”

Section: Discussionmentioning

confidence: 99%

HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺T lymphocytes

Gooden

Lampen²,

Jordanova³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

184

187

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HLA-E is a nonclassical HLA class I molecule, which differs from classical HLA molecules by its nonpolymorphic, conserved nature. Expression and function of HLA-E in normal tissues and solid tumors is not fully understood. We investigated HLA-E protein expression on tissue sections of 420 ovarian and cervical cancers and found equal or higher levels than normal counterpart epithelia in 80% of the tumors. Expression was strongly associated with components of the antigen presentation pathway, e.g., transporter associated with antigen processing (TAP), endoplasmic reticulum aminopeptide (ERAP), β2 microglobulin (β2m), HLA classes I and II, and for ovarian cancer with tumor infiltrating CD8 + T lymphocytes (CTLs). This association argues against the idea that HLA-E would compensate for the loss of classical HLA in tumors. In situ detection of HLA-E interacting receptors revealed a very low infiltrate of natural killer (NK) cells, but up to 50% of intraepithelial CTLs expressed the inhibiting CD94/NKG2A receptor. In cervical cancer, HLA-E expression did not alter the prognostic effect of CTLs, most likely due to very high infiltrating CTL numbers in this virus-induced tumor. Overall survival of ovarian cancer patients, however, was strongly influenced by HLA-E, because the beneficial effect of high CTL infiltration was completely neutralized in the subpopulation with strong HLA-E expression. Interestingly, these results indicate that CTL infiltration in ovarian cancer is associated with better survival only when HLA-E expression is low and that intratumoral CTLs are inhibited by CD94/NKG2A receptors on CTLs in the tumor microenvironment.

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“…Santinet et al (Santin et al, 2001) found a higher expression levels of TGF-β among PBMCs in oophoroma patients. This was similar with the result made in our paper.…”

Section: Discussionmentioning

confidence: 99%

Effects of Gastric Cancer Cells on the Differentiation of Treg Cells

Yang²,

Tang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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The aim of this study was evaluated the prevalence of Treg cells in peripheral blood in patients with gastric cancer, and investigate the effect of gastric cancer cells on their differentiation. ELISA was employed to assess the concentrations of TGF-β and IL-10 in gastric cancer patients' serum. Then, mouse gastric cancer cells were co-cultured with T lymphocytes or T lymphocytes + anti-TGF-β. Flow cytometric analysis and RT-PCR were then performed to detect Treg cells and TGF-β and IL-10 expression in gastric cancer cells. Our data showed that the expression of TGF-β and IL-10 in the patients with gastric cancer was increased compared to the case with healthy donors. The population of Treg cells and the expression levels of TGF-β and IL-10 in the co-culture group were much higher than in the control group (18.6% vs 9.5%) (P<0.05). Moreover, the population of Treg cells and the expression levels of TGF-β and IL-10 in the co-culture systerm were clearly decreased after addition of anti-TGF-β (7.7% vs 19.6%) (P<0.01). In conclusion, gastric cancer cells may induce Treg cell differentiation through TGF-β, and further promote immunosuppression.

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Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer

Cited by 41 publications

References 44 publications

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺T lymphocytes

Effects of Gastric Cancer Cells on the Differentiation of Treg Cells

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Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer

Cited by 41 publications

References 44 publications

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8+T lymphocytes

Effects of Gastric Cancer Cells on the Differentiation of Treg Cells

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HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺T lymphocytes