Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells

Regev, Ofer; Kidan, Noa; Nicola, Meshel; Khamisie, Hazem; Ruthardt, Martin; Mahajna, Jamal

doi:10.5114/aoms.2020.101042

Cited by 9 publications

(12 citation statements)

References 54 publications

(84 reference statements)

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“…As previously reported, cellular and soluble TME compartments play a role in conferring platinum chemoresistance to OC cells [22] , [23] , [24] . Those findings showed that direct co-culture of OC with MSC resulted in conferring chemoresistance to therapeutic drugs such as paclitaxel, colchicine, and platinum compounds, alongside blocking of ERK1/2 activation [22] .…”

Section: Introductionsupporting

confidence: 63%

Ovarian cancer ascites confers platinum chemoresistance to ovarian cancer cells

Carmi,

Agbarya,

Khamaisi

et al. 2024

Translational Oncology

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Section: Introductionsupporting

confidence: 63%

Ovarian cancer ascites confers platinum chemoresistance to ovarian cancer cells

Carmi,

Agbarya,

Khamaisi

et al. 2024

Translational Oncology

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“…As previously reported, cellular and soluble TME compartments play a role in conferring platinum chemoresistance to OC cells (21) (22) (23). Those findings showed that direct co-culture of OC with MSC resulted in conferring chemoresistance to therapeutic drugs such as paclitaxel, colchicine, and platinum compounds, alongside blocking of ERK1/2 activation (21).…”

Section: Introductionsupporting

confidence: 57%

“…4A), implying induction of platinum chemoresistance. The ability of Crizotinib, a multi-kinase inhibitor targeting c-MET, ALK, ROS1 and other kinases (22), to affect platinum chemoresistance in OC cells was investigated. The current results revealed that exposure to Crizotinib caused a significant increase in cPARP levels, implying the restoration of platinum sensitivity.…”

Section: Crizotinib Promotes Rjy13 Sensitivity In Resistant Oc Cells ...mentioning

confidence: 99%

Ascites in malignant ovarian cancer confer ovarian cancer cells chemoresistance to platinum. Combination treatment with crizotinib and 2-hydroxyestradiol restores platinum sensitivity

Carmi,

Agbarya,

Khamaisi

et al. 2023

Preprint

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Ovarian cancer (OC), the second most common form of gynecologic malignancy, has a poor prognosis and is often discovered in the late stages. Platinum-based chemotherapy is the first line of therapy. Nevertheless, treatment OC has proven challenging due to toxicity and the development of acquired resistance to therapy. Tumor microenvironment (TME) has been associated with platinum chemoresistance. Malignant ascites has been used as OC tumor microenvironment and its ability to induce platinum chemoresistance has been investigated. Our results suggest that exposure to OC ascites induces platinum chemoresistance in 11 of 13 cases (85%) on OC cells. In contrast, 75% of cirrhotic ascites (3 of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL -6 and to a lesser extent HGF were enriched in OC ascites, whereas IL -22 was enriched in cirrhotic ascites. Pharmaceutical inhibitors targeting the IL -6/ JAK pathway were mildly effective in overcoming platinum chemoresistance induced by malignant ascites. In contrast, crizotinib, an HGF/c- MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemosensitivity to OC. Our results demonstrate the importance of OC ascites in supporting platinum chemoresistance and the potential of combination therapy to restore chemosensitivity of OC cells.

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“…In this study, we utilized species-selective antibody-recognizing cleaved human Poly(ADP-Ribose Polymerase 1) (PARP1), but not murine cleaved PARP1, to monitor apoptosis induction in OC cells. Levels of cleaved PARP1 were monitored using ELISA or immunoblotting assays [ 27 ] in A2780CisR cells, a cisplatin-resistant OC cell line exposed to our novel prodrug RJY13 [ 26 ]. In an attempt to identify compounds that are active in restoring platinum sensitivity to OC cells directly co-cultured with MSC [ 15 ], a number of pharmaceuticals compounds were included with RJY13 and exposed to OC cells co-cultured with MS-5.…”

Section: Resultsmentioning

confidence: 99%

2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

2022

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Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.

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Mesenchymal soluble factors confer imatinib drug resistance in chronic myelogenous leukemia cells

Cited by 9 publications

References 54 publications

Ovarian cancer ascites confers platinum chemoresistance to ovarian cancer cells

Ovarian cancer ascites confers platinum chemoresistance to ovarian cancer cells

Ascites in malignant ovarian cancer confer ovarian cancer cells chemoresistance to platinum. Combination treatment with crizotinib and 2-hydroxyestradiol restores platinum sensitivity

2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

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