Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells

Petrella, Francesco; Coccè, Valentina; Masia, Carla; Milani, M; Salè, Emanuela Omodeo; Alessandri, Giulio; Parati, Eugenio; Sisto, Francesca; Pentimalli, Francesca; Brini, A.T.; Pessina, Augusto; Spaggiari, Lorenzo

doi:10.1016/j.biopha.2017.01.118

Cited by 37 publications

(36 citation statements)

References 10 publications

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“…Understanding the origin of CA‐MSCs may also have significant therapeutic implications. Given the migratory activity and cancer tropism of MSCs, several studies have proposed using MSCs as therapeutic vehicles . Our study suggests the source of MSCs in these studies is critical—BM MSCs could be effectively used in ovarian cancer but may be a poor source of MSCs for breast cancer studies.…”

Section: Discussionmentioning

confidence: 91%

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

et al. 2018

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Carcinoma‐associated mesenchymal stem cells (CA‐MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA‐MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer “stemness,” and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA‐MSCs to demonstrate global changes in CA‐MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA‐MSCs. Our classifier accurately distinguishes normal omental, ovary, and bone marrow MSCs from ovarian cancer CA‐MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA‐MSCs and distinguishes cancer associated fibroblasts from CA‐MSCs. Using this classifier, we definitively demonstrate ovarian CA‐MSCs arise from tumor mediated reprograming of local tissue MSCs. Although cancer cells alone cannot induce a CA‐MSC phenotype, the in vivo ovarian TME can reprogram omental or ovary MSCs to protumorigenic CA‐MSCs (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA‐MSC phenotype. Interestingly, although the breast cancer TME can reprogram bone marrow MSCs into CA‐MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA‐MSC conversion is tissue and cancer type dependent. Together these findings (a) provide a critical tool to define CA‐MSCs and (b) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. S tem C ells 2019;37:257–269

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Section: Discussionmentioning

confidence: 91%

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

et al. 2018

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“…This peculiar cancer tropism has opened up an emerging field to use MSCs as vectors to deliver antineoplastic drugs for targeted therapies. 8 Mesenchymal stromal cells (MSCs) are a group of undifferentiated multipotent adult cells residing within the human body; they are commonly described as plasticadherent, fibroblast-like cells disclosing clear self-renewal properties and the possibility to differentiate both in vivo and in vitro into a variety of mesenchymal lineage cells; they can differentiate into chondrogenic, osteogenic and adipogenic lineages when adequately cultured in selective media under specific inducing conditions. 52,53 Once inserted in the host tissues, MSCs can interact with the surrounding microenvironment stimulating tissue healing, reparation and regeneration and exerting intense anti-inflammatory and immunomodulatory effects by several different mechanisms.…”

Section: Mpm Mesenchymal Stromal Cell Experimental Treatmentmentioning

confidence: 99%

“…We have previously demonstrated that paclitaxel-primed mesenchymal stromal cells and a cationic platinum(II) complex-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. 8,57 Other thoracic malignancies Although we focused our review on NSCLC and MPM, at least two other thoracic malignancies should also be mentioned to complete the clinical scenario of thoracic oncology: small cell lung cancer and thymic neoplasms.…”

Section: Mpm Mesenchymal Stromal Cell Experimental Treatmentmentioning

confidence: 99%

“…It can occur at any place where mesothelial cells de-differentiate from mesenchymal cells, including the pericardium, peritoneum, tunica vaginalis of the ovary and testis, although both pleurae (visceral and parietal pleura) are the most common affected structures. 8,9 The incidence of MPM in in Japan and Europe are projected to peak in 2025 and 2020 respectively, while the incidence in the USA has remained stable at 3000 deaths per year since peaking in 2004. 10 Surgical resection is the best therapeutic approach in early stages MPM (I, II and selected N0 stage III) without distant diffusion as well as radiotherapy as complementary or symptomatic treatment.…”

Section: Introductionmentioning

confidence: 99%

“…11 A platinum-based doublet with a third-generation antifolate (pemetrexed (PMX) or raltitrexed) is the present front-line standard of care; on the contrary, there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents. 8 Both NSCLC and MPM -although different clinical and epidemiologic entitiesnowadays represent two of the most intriguing and scrutinized thoracic malignancies, presenting interesting perspective of experimental development and daily clinical applications; the aim of the present review is to focus on preclinical and clinical aspects of medical therapy of NSCLC and MPM.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: state of the art and future perspectives

Petrella

Rimoldi

Facchetti

et al. 2018

Expert Opinion on Therapeutic Patents

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Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

Taheri,

Tehrani,

Dehghani

et al. 2024

Medicinal Research Reviews

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Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

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Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells

Cited by 37 publications

References 10 publications

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma

Novel platinum agents and mesenchymal stromal cells for thoracic malignancies: state of the art and future perspectives

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle

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