Patient-derived xenograft models in musculoskeletal malignancies

Lü, Wei; Tu, Chao; Chen, RuiQi; Su, Juan; Li, Zhihong

doi:10.1186/s12967-018-1487-6

Cited by 27 publications

(28 citation statements)

References 88 publications

(110 reference statements)

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ PDX have been so far successfully established and characterized for many different cancer types, such as colorectal 38,39 , pancreatic 40 , lung 41 , breast [42][43][44] , ovarian 45,46 and endometrial cancer 47 . Together with other bone tumor PDX series 17,28,[48][49][50][51][52][53] , the systematic collection of PDX from bone sarcomas, including EW, allows the generation of a wider repository of reliable models for testing drug sensitivity, biomarkers evaluation, or tuning of a personalized therapeutical schedule. A comparison of our series of bone sarcoma PDXs with those recently published by Rainusso et al 53 and Stewart et al 28 shows a lower (but not statistically significant) global percentage of engraftment (32% vs 54% vs 45%, respectively).…”

Section: Discussionmentioning

confidence: 99%

“…www.nature.com/scientificreports www.nature.com/scientificreports/ establishment of bone sarcoma cell cultures from clinical samples and from pDXs. We had the opportunity to obtain tumor material also to seed in vitro primary cultures from most clinical specimens (73 of 90 cases), thus enabling us to directly compare the two major ways to establish human tumor models 10,17,29 .…”

Section: Sanger Analysis Of Tp53 Mutational Status and Assessment Of mentioning

confidence: 99%

“…Any further improvement in the design of innovative therapeutic approaches requires a better understanding of tumor evolution, development of drug resistance and the testing of new compounds in appropriate experimental models [8][9][10][11][12] . Recently the development of patient-derived xenografts (PDXs) obtained by direct implant of surgically resected tumors in immunodeficient mice, has offered a more accurate and reliable preclinical model of cancer 9,[13][14][15][16][17][18] . We present here a new large panel of OS and EW PDX and primary cell cultures obtained from patients treated at IRCCS Istituto Ortopedico Rizzoli, and we show that PDX faithfully mirror the molecular and cellular phenotype of the original human tumor.…”

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Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations

Nanni

Landuzzi

Manara

et al. 2019

Sci Rep

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Standard therapy of osteosarcoma (oS) and ewing sarcoma (eW) rests on cytotoxic regimes, which are largely unsuccessful in advanced patients. preclinical models are needed to break this impasse. A panel of patient-derived xenografts (pDX) was established by implantation of fresh, surgically resected osteosarcoma (OS) and Ewing sarcoma (EW) in NSG mice. Engraftment was obtained in 22 of 61 OS (36%) and 7 of 29 EW (24%). The success rate in establishing primary cell cultures from OS was lower than the percentage of pDX engraftment in mice, whereas the reverse was observed for eW; the implementation of both in vivo and in vitro seeding increased the proportion of patients yielding at least one workable model. the establishment of in vitro cultures from PDX was highly efficient in both tumor types, reaching 100% for EW. Morphological and immunohistochemical (SATB2, P-glycoprotein 1, CD99, caveolin 1) studies and gene expression profiling showed a remarkable similarity between patient's tumor and pDX, which was maintained over several passages in mice, whereas cell cultures displayed a lower correlation with human samples. Genes differentially expressed between OS original tumor and PDX mostly belonged to leuykocyte-specific pathways, as human infiltrate is gradually replaced by murine leukocytes during growth in mice. In EW, which contained scant infiltrates, no gene was differentially expressed between the original tumor and the PDX. A novel therapeutic combination of anti-CD99 diabody C7 and irinotecan was tested against two EW PDX; both drugs inhibited PDX growth, the addition of anti-CD99 was beneficial when chemotherapy alone was less effective. The panel of oS and eW pDX faithfully mirrored morphologic and genetic features of bone sarcomas, representing reliable models to test therapeutic approaches. Osteosarcoma (OS) and Ewing sarcoma (EW), the two most common primary tumors of bone, are high-grade malignant neoplasms with very aggressive behavior and high tendency to form metastasis; they arise frequently in children and remain prominent among teenagers and young adults 1-4 .

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Section: Discussionmentioning

confidence: 99%

Section: Sanger Analysis Of Tp53 Mutational Status and Assessment Of mentioning

confidence: 99%

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Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations

Nanni

Landuzzi

Manara

et al. 2019

Sci Rep

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“…PDXs have been established in various tumor types with varying success rates, ranging from 95% in prostate cancer to 9% in renal cell carcinoma 1,2 . For soft tissue sarcomas, the success rates of PDXs have been reported to be 37.8 to 70.9% 8 . However, only a few gastrointestinal stromal tumor (GIST) PDX models have been reported to date.…”

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confidence: 99%

Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success

Ryu

Park

et al. 2020

Sci Rep

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patient-derived xenografts (pDXs) can represent the heterogeneity and histological characteristics of tumors and are thus useful for testing the efficacy of anti-cancer drugs; however, PDXs are difficult to generate, especially for gastrointestinal stromal tumor (GIST). We analyzed the clinicopathologic factors associated with the successful establishment of GIST PDX in NOD.Cg-Prkdc scid IL2rg tm1Wjl /SzJ mice. We used 185 GIST tumor fragments from patients who underwent surgical resection prior to (n = 66; 35.7%) and after treatment (n = 119; 64.3%) with tyrosine kinase inhibitors. The overall success rate of PDX establishment was 17%; in univariate analysis, engraftment success was associated with after TKI treatment, larger tumor size, higher mitotic count, higher Ki-67 index, higher cellularity, presence of tumor necrosis, primary mutations in KIT exon 11, and originating from metastatic lesions. In multivariate analysis, higher Ki-67 index, after TKI treatment, and larger tumor size were independent factors for engraftment success. Immunohistochemistry in representative samples further corroborated the above results. These results will be useful in the establishment of PDX models from GISTs.

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“…The rarity of the disease makes it difficult to carry out early-phase clinical trials. There is, therefore, a need for appropriate animal models that recapitulate the complexity and the heterogeneity of this malignancy [12].…”

Section: Introductionmentioning

confidence: 99%

Jaw osteosarcoma models in mice: first description

Bertin

Guilho²,

Brion³

et al. 2019

J Transl Med

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Background Osteosarcoma (OS) is the most common cancer of bone. Jaw osteosarcoma (JOS) is rare and it differs from other OS in terms of the time of occurrence (two decades later) and better survival. The aim of our work was to develop and characterize specific mouse models of JOS. Methods Syngenic and xenogenic models of JOS were developed in mice using mouse (MOS-J) and human (HOS1544) osteosarcoma cell lines, respectively. An orthotopic patient-derived xenograft model (PDX) was also developed from a mandibular biopsy. These models were characterized at the histological and micro-CT imaging levels, as well as in terms of tumor growth and metastatic spread. Results Homogeneous tumor growth was observed in both the HOS1544 and the MOS-J JOS models by injection of 0.25 × 10 6 and 0.50 × 10 6 tumor cells, respectively, at perimandibular sites. Histological characterization of the tumors revealed features consistent with high grade conventional osteosarcoma, and the micro-CT analysis revealed both osteogenic and osteolytic lesions. Early metastasis was encountered at day 14 in the xenogenic model, while there were no metastatic lesions in the syngenic model and in the PDX models. Conclusion We describe the first animal model of JOS and its potential use for therapeutic applications. This model needs to be compared with the usual long-bone osteosarcoma models to investigate potential differences in the bone microenvironment. Electronic supplementary material The online version of this article (10.1186/s12967-019-1807-5) contains supplementary material, which is available to authorized users.

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Patient-derived xenograft models in musculoskeletal malignancies

Cited by 27 publications

References 88 publications

Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations

Bone sarcoma patient-derived xenografts are faithful and stable preclinical models for molecular and therapeutic investigations

Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success

Jaw osteosarcoma models in mice: first description

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