Fatty acid synthase expression in osteosarcoma and its correlation with pulmonary metastasis

Abstract

Abstract. Previous experimental evidence has suggested that fatty acid synthase (FASN) may be involved in cancer metastasis. However, its role has been poorly evaluated in osteosarcoma. The aim of this study was to investigate the correlation of FASN expression with pulmonary metastasis and the correlation of FASN expression with the Ki-67 antigen, a proliferation marker, in patients with osteosarcoma of the extremities. The expression of FASN protein and Ki-67 was detected by immunohistochemistry of biopsy tissues from 136 patients with osteosarcoma of the extremities and 21 cases of osteoenchondroma. Positive expression of the FASN protein was observed and located in the cytoplasm. The positive expression rate of FASN was 63.2% in osteosarcoma and 28.6% in osteoenchondroma (p<0.05). The expression levels of the FASN protein were higher in the cases with lung metastasis compared to those without metastasis (p<0.01). The percentage of Ki-67 stained nuclei in osteosarcoma with pulmonary metastasis and in those without was 43.43±10.05 and 25.41±6.68%, respectively (p<0.01). There was a positive correlation between FASN and Ki-67 protein expression in osteosarcoma (Spearman's rho, F=43.05, R=0.734). Therefore, FASN may be a promising target in the treatment of osteosarcoma metastasis.

Natural Compounds as Regulators of the Cancer Cell Metabolism

“…These alterations were initially identified in hormone-dependent malignancies such as those affecting breast [32] and prostate [33], thus confirming the relevance of steroid hormone-dependent pathways in the observed altered lipid metabolism. More recently, comparable patterns of alterations were identified in other cancer cell lines derived from melanoma [34], osteosarcoma [35], colorectal [36, 37], and lung cancer [38], as well as in hematopoietic cancer cells [39, 40]. These cellular environments allowed to identify additional modulatory upstream pathways including mitogen-activated protein kinase-(MAPK-) dependent [41], phosphatidylinositol-3-kinase (PI3K)/Akt pathway [41, 42], H-ras [41] and AMP-activated protein kinase, AMPK [43].…”

“…This dual clinical potential is supported by the observation that FAS inhibitors suppress carcinogenesis in in vivo procarcinogenic models of breast [50] and lung [38] tissues; moreover, they trigger cell death in a number of cancer cell lines [34, 47, 51–53], without affecting normal lipogenic tissues [54]. Additionally, FAS expression correlates with metastasis formation [35] and its targeting alleviates chemoresistance when combined with chemotherapeutic agents [55]. These multiple anticancer activities together with the observation that FAS are overexpressed in premalignant lesions [56, 57] strongly point at a very early role of FAS overexpression in carcinogenesis and led to the speculation that this enzyme may effectively be considered an oncogene [58–60].…”

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

“…Furthermore, chemotherapy cannot effectively control tumor metastasis and progression. Almost 10 years of research has revealed that the survival rate for patients with OS has reached a plateau: The 5-year survival rate remains ~60%, even when combined chemotherapy is used (40). The 5-year survival rate for patients with pulmonary metastases in the early stage of treatment, however, remains lower than 20%.…”

Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models

“…Inhibition of FASN may suppress cancer cell proliferation and metastasis in vitro and in vivo (10)(11)(12)(13)(14). Previous studies have demonstrated that FASN is overexpressed in OS cells and tissues and knockdown of FASN may suppresses the invasion and migratory ability of OS cells by downregulating the human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor (NF)-κB signaling pathway in vitro (15,16); however, the tumor microenvironment has an important influence on tumor progression.…”