Role of CD70 in pathogenesis of ovarian cancer cell metastasis

2018 ◽  
Vol 6 (4) ◽  
pp. 315-322
Author(s):  
Jack L. Pincheira ◽  
Maria Wiseman
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Abdominal Cavity ◽  
Activated T Cells ◽  
Cancer Society ◽  
Tissue Samples

American Cancer Society identifying ovarian carcinoma as the gynecologic malignancy with the highest case-to-fatality. Ovarian carcinoma metastasizes either by direct extension from the ovarian/fallopian tumor to neighboring organs (bladder/colon) or when cancer cells detach from the primary tumor. Exfoliated tumor cells are transported throughout the peritoneum by physiological peritoneal fluid and disseminate within the abdominal cavity. Extensive seeding of the peritoneal cavity by tumor cells is often associated with ascites, particularly in advanced, high-grade serous carcinomas. CD70 (encoded by the TNFSF7 gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. CD70 is over expressed in tumor cells of various solid cancers including ovarian carcinoma, recently reported the role of CD70 expression as a predictive marker of resistance to chemotherapy in ovarian cancers. We evaluated the expression of CD70 level in the pathogenesis of metastasis ovarian cancer cell. Seventy five tissue samples from metastatic ovarian carcinoma were evaluated by quantitative real-time PCR for CD70 and statistical analyses were performed using the Mann-Whitney test. Further, humanized anti-CD70 antibodies were investigated in xenograft mice models of ovarian cancer. Increasing expression of CD70 level was associated with increased risks for disease progression (HR = 1.04; 95% CI, 1.03 to 1.14) and death (HR = 1.13; 95% CI, 1.09 to 1.2). expression of CD70 was associated with a worse PFS and OS compared with non- expression of CD70 carcinomas. Furthermore, humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of ovarian cancer cell.

Role of CD70 in pathogenesis of ovarian cancer cell metastasis

2020 ◽  
Vol 8 (2) ◽  
pp. 101-111
Author(s):  
Jack L. Pincheira ◽  
Maria Wiseman
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Abdominal Cavity ◽  
Activated T Cells ◽  
Cancer Society ◽  
Tissue Samples

Abstract American Cancer Society identifying ovarian carcinoma as the gynecologic malignancy with the highest case-to-fatality. Ovarian carcinoma metastasizes either by direct extension from the ovarian/fallopian tumor to neighboring organs (bladder/colon) or when cancer cells detach from the primary tumor. Exfoliated tumor cells are transported throughout the peritoneum by physiological peritoneal fluid and disseminate within the abdominal cavity. Extensive seeding of the peritoneal cavity by tumor cells is often associated with ascites, particularly in advanced, high-grade serous carcinomas. CD70 (encoded by the TNFSF7 gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. CD70 is over expressed in tumor cells of various solid cancers including ovarian carcinoma, recently reported the role of CD70 expression as a predictive marker of resistance to chemotherapy in ovarian cancers. We evaluated the expression of CD70 level in the pathogenesis of metastasis ovarian cancer cell. Seventy five tissue samples from metastatic ovarian carcinoma were evaluated by quantitative real-time PCR for CD70 and statistical analyses were performed using the Mann-Whitney test. Further, humanized anti-CD70 antibodies were investigated in xenograft mice models of ovarian cancer. Increasing expression of CD70 level was associated with increased risks for disease progression (HR = 1.04; 95% CI, 1.03 to 1.14) and death (HR = 1.13; 95% CI, 1.09 to 1.2). expression of CD70 was associated with a worse PFS and OS compared with non- expression of CD70 carcinomas. Furthermore, humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of ovarian cancer cell.

Interactions of Human Peritoneal Mesothelial Cells With Serous Ovarian Cancer Cell Spheroids—Evidence for a Mechanical and Paracrine Barrier Function of the Peritoneal Mesothelium

2014 ◽  
Vol 24 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Sylvia Stadlmann ◽  
Hans Feichtinger ◽  
Gregor Mikuz ◽  
Christian Marth ◽  
Alain Gustave Zeimet ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cell ◽  
Ovarian Carcinoma ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cell Aggregates ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Peritoneal Mesothelium

BackgroundOvarian carcinoma spreads by implantation of tumor cells onto the peritoneal mesothelium. We established a 3-dimensional coculture model to simulate the interactions of ovarian carcinoma cell aggregates with human peritoneal mesothelial cells (HPMC).MethodsMulticellular tumor spheroids (MCTS) of the human ovarian cancer cell line SK-OV-3 were directly inoculated onto either confluent HPMC monolayers or their submesothelial matrix or were cocultured with mesothelium without direct cellular contact.Results and DiscussionsInoculation of MCTS onto submesothelial matrix resulted in rapid attachment (within 30 minutes) of the tumor cell aggregates followed by rapid dissemination (within 12 hours) and growth of tumor cells. Intact mesothelium increased the time required for MCTS attachment (up to 180 minutes) and led to almost complete inhibition of tumor cell dissemination and to 47% tumor growth suppression. Bromodeoxyuridine incorporation into tumor cell nuclei was almost completely abolished in cocultured MCTS. Growth also was inhibited in MCTS treated with supernatants of HPMC. Analysis of coculture supernatants revealed that HPMC-derived transforming growth factor β (TGF-β) was almost completely bound by MCTS. Addition of a function-blocking anti–TGF-β antibody (30 μg/mL) to the cocultures abrogated the growth inhibitory effect of the mesothelium by 50%.ConclusionsThe present model provides a dynamic system to study the complex interactions of ovarian carcinoma cells with HPMC over extended periods and suggests that the mesothelium constitutes a mechanical and partly TGF-β–mediated paracrine barrier to the progression of ovarian cancer.

scholarly journals The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma

2019 ◽  
Author(s):  
Mikhail Chesnokov ◽  
Imran Khan ◽  
Yeonjung Park ◽  
Jessica Ezel ◽  
Geeta Mehta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Ovarian Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
High Grade ◽  
Tissue Samples ◽  
Serous Ovarian Carcinoma

AbstractRationaleHigh-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to high rate of recurrence and acquired chemoresistance. Mutation and activation of the RAS/MAPK pathway has been linked to cancer cell proliferation and therapeutic resistance in numerous cancers. While RAS mutations are not commonly observed in HGSOC, less is known about downstream pathway activation. We therefore sought to investigate the role of MEK1/2 signaling in ovarian cancer.MethodsMEK1/2 pathway activity was evaluated in clinical HGSOC tissue samples and ovarian cancer cell lines by using tissue microarray-based immunohistochemistry, immunoblotting, and RT-qPCR. OVCAR8 and PEO4 HGSOC cell lines were used to assess the effect of MEK1/2 inhibition on cell viability, proliferation rate, and stem-like characteristics. Xenografts were used in mice to investigate the effect of MEK1/2 inhibition on tumor growth in vivo. A drug washout experimental model was used to study the lasting effects of MEK1/2 inhibition therapy.ResultsMEK1/2 signaling is active in a majority of HGSOC tissue samples and cell lines. MEK1/2 is further stimulated by cisplatin treatment, suggesting that MEK1/2 activation may play a role in chemotherapy resistance. The MEK1/2 inhibitor, trametinib, drastically inhibits MEK1/2 downstream signaling activity, causes prominent cell cycle arrest in the G1/0-phase in cell cultures, and reduces the rate of tumor growth in vivo, but does not induce cell death. Cells treated with trametinib display a high CD133+ fraction and increased expression of stemness-associated genes. Transient trametinib treatment causes long-term increases in a high ALDH1 activity subpopulation of cells that possess the capability of surviving and growing in non-adherent conditions.ConclusionsMEK1/2 inhibition in HGSOC cells efficiently inhibits proliferation and tumor growth and therefore may be a promising approach to suppress ovarian cancer cell growth. MEK1/2 inhibition promotes stem-like properties, thus suggesting a possible mechanism of resistance and that a combination with CSC-targeting drugs should be considered.

The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion

2015 ◽  
Vol 137 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Juanni Li ◽  
Long Li ◽  
Zexia Li ◽  
Guanghui Gong ◽  
Puxiang Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Human Ovarian Cancer ◽  
Cancer Cell Invasion ◽  
Human Ovarian Cancer Cell

scholarly journals Role of notch pathway and HNF1 in cell death induced by HDACs inhibitors in ovarian cancer cell lines, serous and clear cells

2010 ◽  
Vol 4 (S2) ◽  
Author(s):  
Fernanda Silva ◽  
Jacinta Serpa ◽  
Germana Domingues ◽  
Gabriela Silva ◽  
António Almeida ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Notch Pathway ◽  
Cancer Cell Lines ◽  
Clear Cells ◽  
Ovarian Cancer Cell Lines

The activity of the synthetic progestin medroxyprogesterone acetate on the invasive phenotype of ovarian cancer cells

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16003-16003
Author(s):  
R. Gogoi ◽  
M. Kudla ◽  
O. Gill ◽  
K. Horwitz ◽  
D. Fishman
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Medroxyprogesterone Acetate ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Breast ◽  
Breast And Ovarian Cancer ◽  
Invasive Potential

16003 Background: Androgens play an integral role in the physiologic and pathologic processes of the ovary. Yet it has been difficult to study the role of the androgen recptors (AR) separately from the other steroid receptors such as the progesterone receptor (PR) in ovarian cancer. This has been made more complicated because most synthetic progestins such as Medroxyprogesterone acetate (MPA) bind both PR and AR. The objectives of our study were: 1. To create an ovarian cancer cell line constitutively expressing only AR. 2. To compare the role of AR activated by the synthetic progestin MPA vs. the pure androgen dihydrotestosterone (DHT) on the invasiveness of human breast and ovarian cancer cells. 3. To investigate the role of matrix metalloproteases (MMP's) associated with invasion. Methods: ER- and PR- human breast (T47D-Y) and ovarian (OvCa 429) cancer cells were engineered to stably express AR. Immunocytochemistry and western blot analyses confirmed that these breast and ovarian cancer cell lines (called Y-AR and OvCa-AR respectively) are PR-, but AR+. Boyden chamber invasion assays were performed using Y-AR and OvCa-AR cells treated with either vehicle, MPA or DHT. The MMP's associated with invasion were further investigated using zymographic assays. Results: AR activation by either MPA or DHT increased the invasive potential of both breast (p<0.05) and ovarian cancer cells with MPA being significantly more effective than DHT at stimulating invasion. However, regardless of the ligand, activation of AR increases tumor cell invasion. To elucidate the MMP's associated with this activation in OvCa-AR cells, we used zymographic analysis. Interestingly, we found that MPA activation of AR decreases both the total level and activation of MMP-9 compared to DHT and vehicle control. Conclusions: Using our model system we are able to study the role of AR independent of PR on the biology of breast and ovarian cancer cells. Our studies suggest that the use of pharmacological doses of synthetic progestins may actually increase the invasive potential of ovarian cancer cells through AR. We hypothesize that blockade of downstream AR targets or the use of selective AR modulators (SARMS) may be of therapeutic value in the treatment of ovarian cancer. No significant financial relationships to disclose.

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