scholarly journals Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop

Oncotarget ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 6916-6932 ◽  
Author(s):  
Lan G. Coffman ◽  
Yun-Jung Choi ◽  
Karen McLean ◽  
Benjamin L. Allen ◽  
Marina Pasca di Magliano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance ◽  
Human Carcinoma ◽  
Hh Signaling

Role of CD10 expression in endometriosis-associated mesenchymal stem cells on the progression of endometriosis-associated carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5561-5561
Author(s):  
Huda Atiya ◽  
Taylor Orellana ◽  
Lan Gardner Coffman
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Growth ◽  
Tumor Cell ◽  
Chemotherapy Resistance ◽  
Cd10 Expression ◽  
Sphere Formation

5561 Background: Endometriosis-associated carcinomas (EACs) such as ovarian clear cell cancer (OCCC) are rare, aggressive, chemo-resistant malignancies. While endometriosis is a known chronic inflammatory condition, the molecular mechanisms for the malignant transformation of endometriosis is unknown. Mesenchymal stem cells (MSC) are a critical component of the ovarian cancer microenvironment. Cancer cells reprogram MSCs to form carcinoma-associated MSCs (CAMSCs), which promote cancer growth, chemotherapy resistance, and metastases. MSCs are also found within the endometriotic microenvironment. CD10, a surface protein expressed by endometrial stromal cells, is also expressed on endometriosis-associated MSCs (enMSCs). Preliminary data demonstrate CD10 expression is lost in a subset of enMSCs and this loss is correlated with the acquisition of tumor-promoting properties. We hypothesized that the CD10 negative subset of enMSCs behave similarly to CAMSCs and support the growth of OCCC. Methods: EnMSCs were isolated from primary human benign endometriosis deposits involving the ovary or fallopian tubes. Flow cytometry was used to measure surface CD10 expression. We investigated the role of low CD10 enMSCs versus high CD10 enMSCs on OCCC tumor cell growth, chemotherapy resistance and stem-like cell properties in vitro and tumor cell engraftment, growth, and metastases in vivo. Luciferase-expressing OCCC cells were (1) used alone, (2) mixed with low CD10 enMSCs, or (3) mixed with high CD10 enMSCs and injected orthotopically into the ovarian bursa of NSG mice. In vivo imaging system was used to follow tumor progression and metastasis. Results: Our results demonstrated that enMSCs have variable CD10 expression. EnMSCs with low CD10 expression significantly enhanced OCCC proliferation, resistance to cisplatin, and sphere formation compared to OCCC alone. In contrast, high CD10 expressing enMSCs significantly reduce OCCC proliferation and sphere formation. Interestingly, low CD10 enMSCs selectively enhanced OCCC cell growth and had no effect on high grade serious ovarian cancer cell growth. Moreover, a reduction of CD10 expression was observed over time when high CD10 enMSCs were co-cultured with OCCC cells. Our results also showed enhanced tumor engraftment when OCCC cells were co-injected with low CD10 enMSCs to 100% one week post-injection, compared to 40% with OCCC and high CD10 enMSCs and 60% with OCCC alone. Further, mice co-injected with low CD10 enMSCs demonstrated increased metastasis and decreased survival compared to mice co-injected with high CD10 enMSCs. Conclusions: Our results indicate there is a sub population of enMSCs, marked by decreased CD10 expression, which selectively enhances OCCC growth. This highlights the existence of a tumor-promoting stromal cell within endometriosis which may be critical to the formation and propagation of EACs.

scholarly journals In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH+ and CD133+ Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel

2021 ◽  
Vol 22 (6) ◽  
pp. 3019
Author(s):  
Naike Casagrande ◽  
Cinzia Borghese ◽  
Francesco Agostini ◽  
Cristina Durante ◽  
Mario Mazzucato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Chemotherapy Resistance ◽  
Multicellular Spheroids ◽  
Multicellular Tumor Spheroid ◽  
Activated Platelets ◽  
Clinical Responses ◽  
Bona Fide ◽  
Paclitaxel Treatment

A high platelet count is associated with a poor prognosis in ovarian cancer (OvCa). Despite good clinical responses with platinating agents in combination with taxanes, numerous OvCa patients relapse due to chemotherapy resistance. Here, we report that treatment of OvCa cells A2780, OVCAR5 and MDAH with releasate from activated platelets (PR) promoted multicellular tumor spheroid (MCTS) formation. These OvCa-MCTSs had increased percentages of CD133+ and aldehyde dehydrogenase (ALDH)+ cells, bona fide markers of OvCa cancer stem cells (CSCs). PR increased OVCAR5- and MDAH-MCTS viability and decreased the cytotoxic and pro-apoptotic effects of paclitaxel, cisplatin and carboplatin. PR increased the volume of spontaneously formed OVCAR8-MCTSs and counteracted their size reduction due to cisplatin, carboplatin and paclitaxel treatment. PR promoted the survival of ALDH+ and CD133+ OvCa cells during cisplatin, carboplatin and paclitaxel treatment. In conclusion, molecules and growth factors released by activated platelets (EGF, PDGF, TGF-β, IGF and CCL5) may protect tumor cells from chemotherapy by promoting the expansion of ALDH+ and CD133+ OvCa-CSCs, favoring drug resistance and tumor relapse.

scholarly journals CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression

2019 ◽  
Vol 44 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Shan Su ◽  
Xueqin Sun ◽  
Qinghua Zhang ◽  
Zhe Zhang ◽  
Ju Chen
Keyword(s):  
Ovarian Cancer ◽  
Cancer Chemotherapy ◽  
Chemotherapy Resistance

scholarly journals Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 965
Author(s):  
Buddhadev Layek ◽  
Mihir Shetty ◽  
Susheel Kumar Nethi ◽  
Drishti Sehgal ◽  
Timothy K. Starr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Delivery ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Solid Tumors ◽  
Efficient Delivery ◽  
Tumor Tissues ◽  
Specific Accumulation ◽  
Targeting Strategy ◽  
High Binding Affinity

Nanocarriers have been extensively utilized for the systemic targeting of various solid tumors and their metastases. However, current drug delivery systems, in general, suffer from a lack of selectivity for tumor cells. Here, we develop a novel two-step targeting strategy that relies on the selective accumulation of targetable synthetic receptors (i.e., azide moieties) in tumor tissues, followed by delivery of drug-loaded nanoparticles having a high binding affinity for these receptors. Mesenchymal stem cells (MSCs) were used as vehicles for the tumor-specific accumulation of azide moieties, while dibenzyl cyclooctyne (DBCO) was used as the targeting ligand. Biodistribution and antitumor efficacy studies were performed in both orthotopic metastatic and patient-derived xenograft (PDX) tumor models of ovarian cancer. Our studies show that nanoparticles are retained in tumors at a significantly higher concentration in mice that received azide-labeled MSCs (MSC-Az). Furthermore, we observed significantly reduced tumor growth (p < 0.05) and improved survival in mice receiving MSC-Az along with paclitaxel-loaded DBCO-functionalized nanoparticles compared to controls. These studies demonstrate the feasibility of a two-step targeting strategy for efficient delivery of concentrated chemotherapy for treating solid tumors.

scholarly journals Adenovirus platform enhances transduction efficiency of human mesenchymal stem cells: An opportunity for cellular carriers of targeted TRAIL-based TR3 biologics in ovarian cancer

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0190125 ◽  
Author(s):  
Lindsay M. Kuroki ◽  
Xingjian Jin ◽  
Igor P. Dmitriev ◽  
Elena A. Kashentseva ◽  
Matthew A. Powell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Transduction Efficiency

scholarly journals Antitumor Activities of Human Placenta-Derived Mesenchymal Stem Cells Expressing Endostatin on Ovarian Cancer

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e39119 ◽  
Author(s):  
Lan Zheng ◽  
Dongmei Zhang ◽  
Xiancheng Chen ◽  
Li Yang ◽  
Yuquan Wei ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Placenta ◽  
Antitumor Activities
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