Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile

Lis, Raphaël; Touboul, Cyril; Halabi, Najeeb; Madduri, Abishek Sainath; Querleu, Denis; Mezey, Jason G.; Malek, Joel A.; Suhre, Karsten; Rafii, Arash

doi:10.1186/1479-5876-12-59

Cited by 29 publications

(21 citation statements)

References 40 publications

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“…Wang et al [41] showed that the cross talk between ovarian cancer cells and tumor-associated macrophages enhances the ability of endothelial cells to promote the progression of ovarian cancer. Moreover, Lis et al [42] demonstrated that co-culture of ovarian cancer cells in direct cellular contact with mesenchymal stem cells induces broad transcriptomic changes related to cellular adhesion, invasion, migration, proliferation and chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation

Mielczarek‐Palacz

Sikora

Kondera-Anasz

et al. 2016

aoms

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IntroductionInterleukin(IL)-1β, IL-6 and IL-12 might associate with inflammatory processes in a tumor progression and create a specific microenvironment for tumor growth. The aim of the study was to assess whether the Th1 and Th2 type cytokines, such as IL-2 and IL-10, affect ovarian carcinoma continuous cell line (SKOV-3) pro-inflammatory activation.Material and methodsSKOV-3 ovarian cells and peripheral blood mononuclear cells (PBMCs) were stimulated by IL-2 and IL-10. Additionally, SKOV-3 ovarian cells and PBMCs were co-cultured together. Proinflammatory activation of cancer cells was evaluated by measurement of IL-1β and IL-6 levels in culture fluid after 72 h of incubation.ResultsSKOV-3 cells and PBMCs secreted IL-1β and IL-6. After stimulation by IL-2 and IL-10, secretion of studied parameters was changed in a dose-dependent manner. The addition of a higher IL-2 level gave rise to an increase of IL-1β, IL-6 and IL-12 secretion in SKOV-3 cells. Stimulation by IL-10 increased only IL-1β secretion in SKOV-3 cells. However, IL-6 secretion decreased after stimulation with 25 ng/ml IL-10. Activatory effects of IL-2 and inhibitory effects of IL-10 in co-culture of SKOV-3 and PBMCs were observed.ConclusionsOur results suggested that Th1/Th2 type of cytokines might influence pro-inflammatory activation of SKOV-3 ovarian cells. Co-cultures of SKOV-3 and PBMCs showed significant changes in cross-talk between cancer and immune cells.

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Section: Discussionmentioning

confidence: 99%

Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation

Mielczarek‐Palacz

Sikora

Kondera-Anasz

et al. 2016

aoms

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“…Ovarian stroma plays an essential role in the normal functioning of the organ, supporting follicle growth and development [ 9 , 10 ]. Recent data indicate that the stroma may be important for tumorigenesis [ 11 ] and invasiveness in ovarian cancer due to the paracrine interaction between cancer-associated fibroblasts (CAFs) and ovarian cancer cells [ 12 - 15 ].…”

Section: Introductionmentioning

confidence: 99%

Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

et al. 2016

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Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features.Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8).In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer.

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“…In this context, previous research has demonstrated a protective role of MSC for cervical tumor cells (35). Interaction of MSC with ovarian cancer cells also contributed to increased metastatic ability (36). More importantly, co-cultures of MSC with SCCOHT-1 GFP cells revealed a significantly elevated resistance of the tumor cells against the cytotoxic action of FK228 alone or a combination of foretinib/FK228 when compared to a SCCOHT-1 GFP mono-culture which further confirmed tumor-protective mechanisms of MSC.…”

Section: Discussionmentioning

confidence: 89%

SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment

Otte

Yang

Ohe

et al. 2016

International Journal of Oncology

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Chemotherapeutic drug testing of SCCOHT-1 and BIN-67 tumor cells revealed synergistic growth-inhibition of >95% in vitro with a combination of foretinib and FK228. Application of this drug combination in vivo in NODscid mice-induced SCCOHT-1GFP tumors was associated with ~6-fold reduction in tumor mass within 10 days, whereby synergistic effects of the two compounds remained undetectable compared to previous results with foretinib treatment alone. Histopathologic evaluation revealed a reduced vascularization and a lower amount of proliferating cells in the treated tumors. Surprisingly, a simultaneous significant accumulation of extracellular matrix structures with positive elastin-van Gieson staining was observed following foretinib/FK228 exposure. Expression analysis of treated animal tumors exhibited various changes including increased mouse transcript levels of elastin, laminin, and fibronectin. In parallel, markers for mesenchymal stroma/stem cells (MSC) including CD73 and CD90 were detectable in all mouse tumors suggesting a possible involvement of these cells in extracellular matrix restructure. Indeed, incubation of MSC with FK228 or foretinib/FK228 demonstrated morphologic alterations and enhanced expression of laminin and fibronectin. Moreover, a co-culture of MSC with lentiviral-labeled SCCOHT-1GFP cells contributed to protection of the tumor cells against FK228-mediated cytotoxicity. Furthermore, explant cultures of SCCOHT-1GFP-induced tumors acquired an increased resistance to FK228 and a combination of foretinib/FK228 in contrast to foretinib alone. Together, these data suggested that FK228-mediated extracellular matrix protein expression by MSC contributes to increased protection and enhanced resistance of SCCOHT tumors which could represent a more general mechanism of MSC during drug-induced alterations of a tumor microenvironment.

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Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile

Cited by 29 publications

References 40 publications

Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation

Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation

Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

SCCOHT tumors acquire chemoresistance and protection by interacting mesenchymal stroma/stem cells within the tumor microenvironment

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