Oncotarget: Development & characterization of COS-33 with activation of mTOR pathway


Oncotarget recently published "Development and characterization of the novel human osteosarcoma cell line COS-33 with sustained activation of the mTOR pathway" which reported that the successful establishment of a new human osteosarcoma cell line, COS-33, from a patient-derived xenograft and demonstrate retention of the biological features of the original tumor.

The Oncotarget authors found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor, rapamycin, a suppressor of the mTOR pathway.

They observed significant inhibitory effects of the drug on cell migration, invasion, and colony formation in the cultured cells.

Furthermore, they found that only a strong osteogenic inducer, bone morphogenetic protein-2, promoted the cells to differentiate into mature mineralizing osteoblasts, indicating that the COS-33 cell line may have impaired osteoblast differentiation.

Grafted COS-33 cells exhibited features typical of osteosarcoma, such as the production of osteoid and tumorigenicity in vivo.

Grafted COS-33 cells exhibited features typical of osteosarcoma, such as the production of osteoid and tumorigenicity in vivo

Dr. Jianning Tao, affiliated with The Cancer Biology and Immunotherapies Group at Sanford Research as well as The South Dakota State University and The University of South Dakota said, "Osteosarcoma (OS) is the most common primary bone cancer in adolescents and in the elderly".

Recent genomic studies with patient tumor samples and models of the human OS have improved our understanding of the disease etiology and have also provided a road map for drug development.

OS cell lines, which are excellent experimental systems, are important for basic and preclinical studies as they allow the investigation of general cell biology and drug discovery.

Figure 8: Photographs of histological sections of COS-33 tumors and the xenograft mouse.

Figure 8: Photographs of histological sections of COS-33 tumors and the xenograft mouse. (AB) Representative images of hematoxylin-and-eosin (H&E) stained section of the parental PDX tumor from which the COS-33 cells were derived. (CE) Representative images of H&E stained section of the COS-33 cell-line-grafted tumor and a tumor-bearing nude mouse (E). The objective magnification 10×(A and C) and 20×(B and D).

Since the establishment of the first human OS cell line, named U-2 OS, in 1967, many human OS cell lines, such as SJSA-1, MG-63, and Saos-2, have been successfully established and characterized.

Over the past 30 years, numerous groups have used models of PDXs for basic and preclinical studies, including the Pediatric Preclinical Testing Consortium, previously known as the Pediatric Preclinical Testing Program.

In this study, the authors report the successful establishment of a novel human OS cell line derived from OS-33, herein designated COS-33, and demonstrate retention of the biological features and drug sensitivity of the original PDX tumors.

The Tao Research Team concluded in their Oncotarget Research Paper, "we established a novel permanent human cancer cell line, COS-33, originating from a female patient who was diagnosed with otsteoblastic OS. The cell line retains the characteristics of the original tumor, including histopathology, cytogenetic complexity, osteoblastic activity, and drug sensitivity. The COS-33 cell line can serve as a new model for investigating the etiology and molecular pathogenesis of OS and for testing novel drugs for treatment."

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DOI - https://doi.org/10.18632/oncotarget.27611

Full text - https://www.oncotarget.com/article/27611/text/

Correspondence to - Jianning Tao - [email protected]

Keywords - osteosarcoma, COS-33, mTOR, osteogenic differentiation, TP53

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