Secretome of human bone marrow mesenchymal stem cells: an emerging player in lung cancer progression and mechanisms of translation initiation

Attar-Schneider, Oshrat; Zismanov, Victoria; Drucker, Liat; Gottfried, Maya

doi:10.1007/s13277-015-4304-3

Cited by 41 publications

(27 citation statements)

References 46 publications

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“…Therefore, treatment options are still limited and the prognosis of these patients is still poor (16). It is imperative to develop novel and more effective therapeutic drugs for the treatment of SCLC patients (17).…”

Section: Discussionmentioning

confidence: 99%

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

Wang

Zhao

Liu

et al. 2016

International Journal of Oncology

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Abstract. Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC. IntroductionLung cancer remains the most common cause of cancer-related death worldwide, and was responsible for 1.56 million deaths annually, as of 2012 (1). The main primary types are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Compared with NSCLC, SCLC has a more aggressive behavior due to its higher proliferative index and tends to spread in its early stages. Combination chemotherapy, generally platinumbased plus etoposide or irinotecan, is the mainstay first-line treatment for metastatic SCLC patients (2,3). Despite the initial sensitivity, the long-term outcomes of the majority of SCLC patients remain poor due to early relapse and acquired resistance (2). In addition, the vast majority of patients with SCLC fail to respond to tyrosine-kinase inhibitors against the epidermal growth factor receptor (EGFR) (4). Except for topotecan, few treatment options then remain (2,5,6). Therefore, it is urgent to develop novel and more effective therapeutic drugs for the treatment of SCLC patients. Doxycycline (DOXY) is a member of the tetracycline family of antibiotics in widespread clinical use. Accumulating evidence has suggested that doxycycline has antitumor activity against several kinds of malignancies. It has been reported that doxycycline has anti-metastatic activity and cytotoxicity in melanoma ...

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Section: Discussionmentioning

confidence: 99%

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

Wang

Zhao

Liu

et al. 2016

International Journal of Oncology

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“…Interestingly, it is important to emphasize that this effect is closely correlated with MSCs tissue of origin (Figure ). As reported by Attar‐Schneider et al, 2015, BM‐MSCs can reduce both cellular proliferation, viability and migration of non‐small lung cancer cells as a result of the down regulation of translation initiation factors and mitogen‐activated protein kinases (MAPK) signaling . However, the same is not true for Wharton jelly‐derived MSCs which show antagonistic effects to those portrayed by BM‐MSCs in lung cancer stem cells (L‐CSCs), acting in a pro‐tumorigenic manner .…”

Section: The Dual Role Of Mesenchymal Stem Cells In the Heterogeneousmentioning

confidence: 97%

“…As reported by Attar-Schneider et al, 2015, BM-MSCs can reduce both cellular proliferation, viability and migration of non-small lung cancer cells as a result of the down regulation of translation initiation factors and mitogen-activated protein kinases (MAPK) signaling. [35] However, the same is not true for Wharton jelly-derived MSCs which show antagonistic effects to those portrayed by BM-MSCs in lung cancer stem cells (L-CSCs), acting in a pro-tumorigenic manner. [32] Conversely, conditioned media derived from human fetal MSCs showed high levels of insulin growth factor binding proteins (IGFBP), which when used in hepatocellular carcinoma cell culture, ends up sequestering free IGF, inhibiting cancer cell proliferation.…”

Section: The Dual Role Of Mesenchymal Stem Cells In the Heterogeneousmentioning

confidence: 99%

Mesenchymal Stem Cells Relevance in Multicellular Bioengineered 3D In Vitro Tumor Models

Ferreira

Gaspar

Henrique

et al. 2017

Biotechnology Journal

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In vitro 3D tumor microenvironment mimicking models are gathering momentum as alternatives to traditional 2D flat monolayer cultures due to their potential for recapitulating major cancer hallmarks. To fulfill such potential, it is crucial that 3D tumor testing platforms completely emulate in vitro the complex in vivo tumor niche and its cellular constituents. Mesenchymal stem cells (MSCs) are recognized to play a pivotal multi-modulatory role in cancer, generating interest as biological targets and as key tumor suppressing, or tumor promoting effectors. This review discusses the biological influence of different types of MSCs in the tumor microenvironment and showcases recent studies that engineer 3D MSCs-cancer cells co-cultures as advanced in vitro therapy testing platforms. A special focus is given to MSCs-cancer 3D co-culture set-up parameters, challenges, and future opportunities. Understanding cancer-MSCs crosstalk and their underlying effects is envisioned to support the development of advanced 3D in vitro disease models for discovery of forefront cancer treatments.

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“…Indeed, BM-MSCs may directly affect the malignancy cancer cells (Karnoub et al, 2007;Xu et al, 2009), support tumour angiogenesis (Au et al, 2008;Suzuki et al, 2011), differentiate into other pro-tumourigenic stromal cells, such as cancer-associated fibroblasts (CAFs) and cancer-associated macrophages (CAMs) (Barcellos- de-Souza et al, 2016;Mishra et al, 2008), and act as immune-modulators to suppress both innate and adaptive immune responses against cancer (Nauta and Fibbe, 2007;Sotiropoulou and Papamichail, 2007). However, there is also evidence indicating an anti-tumoural activity of BM-MSCs (Attar-Schneider et al, 2016;Lee et al, 2013;Qiao et al, 2008). Indeed, the role of BM-MSCs in promoting tumourigenesis is still controversial and warrants further studies.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow‐derived mesenchymal stem cells promote invasiveness and transendothelial migration of osteosarcoma cells via a mesenchymal to amoeboid transition

et al. 2018

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There is growing evidence to suggest that bone marrow‐derived mesenchymal stem cells (BM‐MSCs) are key players in tumour stroma. Here, we investigated the cross‐talk between BM‐MSCs and osteosarcoma (OS) cells. We revealed a strong tropism of BM‐MSCs towards these tumour cells and identified monocyte chemoattractant protein (MCP)‐1, growth‐regulated oncogene (GRO)‐α and transforming growth factor (TGF)‐β1 as pivotal factors for BM‐MSC chemotaxis. Once in contact with OS cells, BM‐MSCs trans‐differentiate into cancer‐associated fibroblasts, further increasing MCP‐1, GRO‐α, interleukin (IL)‐6 and IL‐8 levels in the tumour microenvironment. These cytokines promote mesenchymal to amoeboid transition (MAT), driven by activation of the small GTPase RhoA, in OS cells, as illustrated by the in vitro assay and live imaging. The outcome is a significant increase of aggressiveness in OS cells in terms of motility, invasiveness and transendothelial migration. In keeping with their enhanced transendothelial migration abilities, OS cells stimulated by BM‐MSCs also sustain migration, invasion and formation of the in vitro capillary network of endothelial cells. Thus, BM‐MSC recruitment to the OS site and the consequent cytokine‐induced MAT are crucial events in OS malignancy.

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Secretome of human bone marrow mesenchymal stem cells: an emerging player in lung cancer progression and mechanisms of translation initiation

Cited by 41 publications

References 46 publications

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer

Mesenchymal Stem Cells Relevance in Multicellular Bioengineered 3D In Vitro Tumor Models

Bone marrow‐derived mesenchymal stem cells promote invasiveness and transendothelial migration of osteosarcoma cells via a mesenchymal to amoeboid transition

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