Targeting the VEGF Pathway in Osteosarcoma

Assi, Tarek; Watson, Sarah; Samra, Bachar; Rassy, Elie El; Cesne, Axel Le; Italiano, Antoîne; Mir, Olivier

doi:10.3390/cells10051240

Cited by 36 publications

(33 citation statements)

References 79 publications

(90 reference statements)

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“…40 VEGF is thought to be produced by cells, such as, tumor cells, macrophages, and platelets and acts on various cell types predominately ECs. 39,41 In normal physiological conditions, VEGF participates in angiogenesis during embryonic development and is crucial for adult wound healing in humans. 42 VEGF is also important in disease progression and is reported to promote tumor growth and metastasis by its involvement in pathological angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma

Feleke

Feng

Song

et al. 2022

Exp Biol Med (Maywood)

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Dysregulation of angiogenesis is associated with tumor development and is accompanied by altered expression of pro-angiogenic factors. EGFL7 is a newly identified antigenic factor that plays a role in various cancers such as breast cancer, lung cancer, and acute myeloid leukemia. We have recently found that EGFL7 is expressed in the bone microenvironment, but its role in giant-cell tumor of bone (GCTB) and osteosarcoma (OS) is unknown. The aims of this study are to examine the gene expression profile of EGFL7 in GCTB and OS and compare with that of VEGF-A-D and TNFSF11 using single-cell RNA sequencing data. In-depth differential expression analyses were employed to characterize their expression in the constituent cell types of GCTB and OS. Notably, EGFL7 in GCTB was expressed at highest levels in the endothelial cell (EC) cluster followed by osteoblasts, myeloid cells, and chondrocytes, respectively. In OS, EGFL7 exhibited highest expression in EC cell cluster followed by osteoblastic OS cells, myeloid cells 1, and carcinoma associated fibroblasts (CAFs), respectively. In comparison, VEGF- A is expressed at highest levels in myeloid cells followed by OCs in GCTB, and in myeloid cells, and OCs in OS. VEGF- B is expressed at highest levels in chondrocytes in GCTB and in OCs in OS. VEGF- C is strongly enriched in ECs and VEGF-D is expressed at weak levels in all cell types in both GCTB and OS. TNFSF11 (or RANKL) shows high expression in CAFs and osteoblastic OS cells in OS, and osteoblasts in GCTB. This study investigates pro-angiogenic genes in GCTB and OS and suggests that these genes and their expression patterns are cell-type specific and could provide potential prognostic biomarkers and cell type target treatment for GCTB and OS.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma

Feleke

Feng

Song

et al. 2022

Exp Biol Med (Maywood)

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“…In addition, the results obtained experimentally illustrate the biological effectivity of the VEGF inhibitors in osteosarcoma, but results in clinical trials indicate that they are modest and transient. [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations

et al. 2022

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Osteosarcoma is a primary malignant bone tumor usually arising at the metaphysis of long bones, particularly around the knee. The physis has been regarded as a barrier capable of blocking tumor extension, thus allowing it to preserve their epiphysis and therefore improve functional results. With the objective of clarifying how effective the physis is as a barrier to tumor spread, a large series of skeletally immature patients with osteosarcoma were reviewed. From 452 metaphyseal osteosarcomas a selection of 282 cases in which the tumor was close or crossing the physis were carried out. This sub-sample was split into two groups according to the surgical treatment (epiphyseal preservation or not). The specimens obtained by resection were studied, and the physeal and metaphyseal areas were studied by multiple sections. Immunostaining against VEGF of physis was obtained in selected cases. In about half of the patients affected by metaphyseal malignant bone tumors, the growth plate and epiphysis were not compromised by the tumor. Three sequential invasive growth patterns of an osteosarcoma in its relationship with the physis could be distinguished. An intense angiogenesis and osteoclastic reaction could be observed in the growth plate in the free zone between the tumor and the physis. The local recurrence incidence was lower in the epiphyseal preservation treated patients than it was in the conventional treatment (8% vs. 12%). Most local recurrences appeared in the first 2 years. The overall survival of patients treated with epiphyseal preservation was better than that of the patients treated without preserving the epiphysis (73% vs. 59%; p = 0.03) at a mean follow-up of 18 years. We have described an angiogenic and osteoclastic reaction in the base of the growth plate in the proximity of the advance front of the tumor, which could facilitate the osteosarcoma invasion. It is also shown that the preoperative imaging method for examination is a valid approach for the decision to carry out epiphyseal preservation. Finally, we concluded that epiphyseal preservation combined with protective chemotherapy is an excellent clinical approach for selected patients with metaphyseal osteosarcoma.

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“…In the elderly, it is often distributed in the axial skeleton and skull (Rickel et al, 2017). According to pathological subtypes, osteosarcoma is classified as osteoblastic, and the most popular subtypes are chondroblastic, fibroblastic, telangiectatic, small cell, surface, and secondary subtypes (Assi et al, 2021). Relapsing or metastatic patients with osteosarcoma have a dismal prognosis with a median overall survival of less than 8 months Frontiers in Genetics frontiersin.org (Lagmay et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression of SPAG6 and NM23 predicts poor prognosis of human osteosarcoma

et al. 2022

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Objective: To investigate the expression and clinical significance of sperm-associated antigen 6 and NM23 proteins in human osteosarcoma.Methods: The specimens of conventional osteosarcoma with follow-up from 42 Chinese patients were analyzed in this study, and 12 cases of osteochondroma were considered controls. The expression of SPAG6 and NM23 was inspected using immunohistochemical staining, qRT-PCR, and Western blotting methods.Results: The positive expression rate of SPAG6 protein (71.43%) in 42 cases of osteosarcoma tissue was significantly higher than that (33.33%) in 12 cases of osteochondroma tissues (p < 0.05), while the positive rate of NM23 protein (35.71%) in osteosarcoma tissue was lower than that (58.33%) in osteochondroma tissue (p < 0.05). The mRNA and protein levels of SPAG6 were significantly higher than those of the adjacent normal tissues, while the expression of NM23 was lower in osteosarcoma tissues than that in the controls (p < 0.05 for all). There was a positive relationship between the expression of SPAG6 and pathological grade, metastasis, and Enneking stage (p < 0.05 for all). The overall survival rate of osteosarcoma patients with SPAG6 positive expression was significantly lower than that with SPAG6 negative expression. The relationship between the expression of NM23 and pathological grade, metastasis, and Enneking stage was negative (p < 0.05 for all). The overall survival rate of the osteosarcoma patients with NM23 positive expression was higher than that of the patients with NM23 negative expression (p < 0.05).Conclusion: Overexpression of SPAG6 and low expression of NM23 are negatively related to pathological grade, metastasis, and Enneking stage and prognosis of osteosarcoma patients. This suggested that SPAG6 and NM23 should be considered candidate prognostic biomarkers for patients with osteosarcoma.

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Targeting the VEGF Pathway in Osteosarcoma

Cited by 36 publications

References 79 publications

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma

Single-cell RNA sequencing reveals differential expression of EGFL7 and VEGF in giant-cell tumor of bone and osteosarcoma

A Reassessment of the Barrier Effect of the Physis against Metaphyseal Osteosarcoma: A Comprehensive Pathological Study with Its Radiological and Clinical Follow-Up Correlations

Aberrant expression of SPAG6 and NM23 predicts poor prognosis of human osteosarcoma

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