scholarly journals The Role of Tumor-Associated Macrophages in the Progression and Chemoresistance of Ovarian Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1299 ◽  
Author(s):  
Marek Nowak ◽  
Magdalena Klink

Tumor-associated macrophages (TAMs) constitute the main population of immune cells present in the ovarian tumor microenvironment. These cells are characterized by high plasticity and can be easily polarized by colony-stimulating factor-1, which is released by tumor cells, into an immunosuppressive M2-like phenotype. These cells are strongly implicated in both the progression and chemoresistance of ovarian cancer. The main pro-tumoral function of M2-like TAMs is the secretion of a variety of cytokines, chemokines, enzymes and exosomes that reach microRNAs, directly inducing the invasion potential and chemoresistance of ovarian cancer cells by triggering their pro-survival signaling pathways. The M2-like TAMs are also important players in the metastasis of ovarian cancer cells in the peritoneum through their assistance in spheroid formation and attachment of cancer cells to the metastatic area—the omentum. Moreover, TAMs interplay with other immune cells, such as lymphocytes, natural killer cells, and dendritic cells, to inhibit their responsiveness, resulting in the development of immunosuppression. The detrimental character of the M2-like type of TAMs in ovarian tumors has been confirmed by a number of studies, demonstrating the positive correlation between their high level in tumors and low overall survival of patients.

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770550 ◽  
Author(s):  
Yi Li ◽  
Ming Xiao ◽  
Fangchun Guo

SOX6 plays important roles in cell proliferation, differentiation, and cell fate determination. It has been confirmed that SOX6 is a tumor suppressor and downregulated in various cancers, including esophageal squamous cell carcinoma, hepatocellular carcinoma, and chronic myeloid leukemia. Netrin-1 is highly expressed in various human cancers and acts as an anti-apoptotic and proangiogenic factor to drive tumorigenesis. The role of SOX6 and netrin-1 in regulating the growth of ovarian tumor cells still remains unclear. Real-time polymerase chain reaction and western blot were used to determine the SOX6 messenger RNA and protein levels, respectively, in ovarian cancer cells and tumor tissues. Stable transfection of SOX6 was conducted to overexpress SOX6 in PA-1 and SW626 cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Invasion of ovarian cancer cells and migration of human umbilical vein endothelial cells were confirmed by Transwell assays. To overexpress netrin-1, ovarian cancer cells with SOX6 restoration was transduced with netrin-1 lentiviral particles. PA-1 xenografts in a nude mice model were used to conduct in vivo evaluation of the role of SOX6 and its relationship with netrin-1 in tumor growth and angiogenesis. In this study, we found significantly reduced SOX6 levels in PA-1, SW626, SK-OV-3, and CaoV-3 ovarian cancer cell lines and human tumor tissues in comparison with normal human ovarian epithelial cells or matched non-tumor tissues. SOX6 overexpression by stable transfection dramatically inhibited proliferation and invasion of PA-1 and SW626 cells. Also, conditioned medium from PA-1 and SW626 cells with SOX6 restoration exhibited reduced ability to induce human umbilical vein endothelial cells migration and tube formation compared with conditioned medium from the cells with transfection control. Furthermore, an inverse relationship between SOX6 and netrin-1 expression was observed in PA-1 and SW626 cells. Overexpression of netrin-1 in ovarian cancer cells with forced SOX6 expression remarkably abrogated the inhibitory effect of SOX6 on proliferation, invasion of the cells, and tumor xenograft growth and vascularity in vivo. Human umbilical vein endothelial cell migration and tube formation were enhanced in the conditioned medium from the ovarian cancer cells transduced with netrin-1 lentivirus particles. Our observations revealed that SOX6 is a tumor suppressor in ovarian cancer cells, and SOX6 exerts an inhibitory effect on the proliferation, invasion, and tumor cell-induced angiogenesis of ovarian cancer cells, whereas nerin-1 plays an opposite role and its expression is inversely correlated with SOX6. Moreover, our findings suggest a new role of SOX6 and netrin-1 for understanding the progression of ovarian cancer and have the potential for the development of new diagnosis and treatment strategies for ovarian cancer.


2010 ◽  
pp. P1-9-P1-9
Author(s):  
J Tang ◽  
P Li ◽  
AKW Tse ◽  
SV Nicosia ◽  
X Zhang ◽  
...  

2020 ◽  
Vol 177 ◽  
pp. 113965
Author(s):  
Shang-Lang Huang ◽  
Ting-Chang Chang ◽  
Chuck C.K. Chao ◽  
Nian-Kang Sun

2020 ◽  
Vol 9 (4) ◽  
pp. 1185 ◽  
Author(s):  
Martha Baydoun ◽  
Olivier Moralès ◽  
Céline Frochot ◽  
Colombeau Ludovic ◽  
Bertrand Leroux ◽  
...  

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.


2011 ◽  
Vol 25 (8) ◽  
pp. 1712-1720 ◽  
Author(s):  
Aneta Rogalska ◽  
Arkadiusz Gajek ◽  
Marzena Szwed ◽  
Zofia Jóźwiak ◽  
Agnieszka Marczak

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