Characterization of 11 human sarcoma cell strains

Hu, Mei; Nicolson, Garth L.; Trent, Jonathan C.; Yu, Dihua; Zhang, Lianglin; Lang, Aiqing; Killary, Ann M.; Ellis, Lee M.; Bucana, Corazon D.; Pollock, Raphael E.

doi:10.1002/cncr.10879

Cited by 9 publications

(4 citation statements)

References 25 publications

(26 reference statements)

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“…Mesenchymal cell-like morphology in sarcoma primary cultures has been noted in early studies from this institution (34). Attempts to culture sarcoma samples often yield non-tumor-forming, cytogenetically normal cultures; this has been proposed as an explanation for the paucity of sarcoma cell lines(35). …”

Section: Discussionmentioning

confidence: 99%

Benign Mesenchymal Stromal Cells in Human Sarcomas

Morozov

Downey

Healey

et al. 2010

Clinical Cancer Research

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Purpose Recent evidence suggests that at least some sarcomas arise through aberrant differentiation of mesenchymal stromal cells (MSCs), but MSCs have never been isolated directly from human sarcoma specimens. Experimental Design We examined human sarcoma cell lines and primary adherent cultures derived from human sarcoma surgical samples for features of MSCs. We further characterized primary cultures as either benign or malignant by the presence of tumor-defining genetic lesions and tumor formation in immunocompromised mice. Results We show that a dedifferentiated liposarcoma cell line DDLS8817 demonstrates fat, bone and cartilage trilineage differentiation potential characteristic of MSCs. Primary sarcoma cultures have the morphology, surface immunophenotype and differentiation potential characteristic of MSCs. Surprisingly, many of these cultures are benign as they do not form tumors in mice and lack sarcoma-defining genetic lesions. Consistent with the recently proposed pericyte origin of MSCs in normal human tissues, sarcoma-derived benign MSCs express markers of pericytes and cooperate with endothelial cells in tube formation assays. In human sarcoma specimens, a subset of CD146-positive microvascular pericytes express CD105, an MSC marker, while malignant cells largely do not. In an in vitro co-culture model, sarcoma-derived benign MSCs as well as normal human pericytes markedly stimulate the growth of sarcoma cell lines. Conclusions Sarcoma-derived benign MSCs/pericytes represent a previously undescribed stromal cell type in sarcoma which may contribute to tumor formation.

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Section: Discussionmentioning

confidence: 99%

Benign Mesenchymal Stromal Cells in Human Sarcomas

Morozov

Downey

Healey

et al. 2010

Clinical Cancer Research

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“…In contrast, low plasma FGF2 levels prior to surgery have been associated with an increased risk of recurrence [9-12]. FGF2 presence has also been confirmed in studies of sarcoma cell-lines [13]. …”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients

et al. 2011

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BackgroundNon-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study investigates the prognostic impact of FGF2 and FGFR-1 and explores the impact of their co-expression with PDGF-B and VEGFR-3 in widely resected tumors from non-GIST STS patients.MethodsTumor samples from 108 non-GIST STS patients were obtained and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expressions of FGF-2, FGFR-1, PDGF-B and VEGFR-3.ResultsIn the multivariate analysis, high expression of FGF2 (P = 0.024, HR = 2.2, 95% CI 1.1-4.4) and the co-expressions of FGF2 & PDGF-B (overall; P = 0.007, intermediate; P = 0.013, HR = 3.6, 95% CI = 1.3-9.7, high; P = 0.002, HR = 6.0, 95% CI = 2.0-18.1) and FGF2 & VEGFR-3 (overall; P = 0.050, intermediate; P = 0.058, HR = 2.0, 95% CI = 0.98-4.1, high; P = 0.028, HR = 2.6, 95% CI = 1.1-6.0) were significant independent prognostic indicators of poor disease-specific survival.ConclusionFGF2, alone or in co-expression with PDGF-B and VEGFR-3, is a significant independent negative prognosticator in widely resected non-GIST STS patients.

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“…These cells formed colonies in clonogenic soft-agar assays and developed tumors upon subcutaneous injection into nude mice. In 2002, additional cell lines were established, the majority from lung metastatic specimens derived from different sarcoma subtypes ( 50 ). In this study, all 11 cell lines analyzed expressed VEGF and basic-FGF, and they grew in anchorage-independent conditions.…”

Section: Two-dimensional (2d) In Vitro Modelsmentioning

confidence: 99%

Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

Gaebler

Silvestri²,

Haybaeck

et al. 2017

Front. Oncol.

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Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

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Characterization of 11 human sarcoma cell strains

Cited by 9 publications

References 25 publications

Benign Mesenchymal Stromal Cells in Human Sarcomas

Benign Mesenchymal Stromal Cells in Human Sarcomas

Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients

Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

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