Establishment of humanised xenograft models as in vivo study for lung metastasis of osteosarcoma

Author:

Khamarudin Farhana12ORCID,Muhamad Mudiana1,Johari Ibahim Mohamad1,Wan Mohamad Zain Wan Nor I’zzah1,Aziz Mardiana Abdul3,Adib Ridzuan Nurul Raudzah4,Ab-Rahim Sharaniza1

Affiliation:

1. Department of Biochemistry and Molecular Medicine, Universiti Teknologi MARA , Sungai Buloh, 47000 Selangor , Malaysia

2. Institute for Medical Molecular Biotechnology, Universiti Teknologi MARA , Sungai Buloh, 47000 Selangor , Malaysia

3. Department of Pathology, Universiti Teknologi MARA , Sungai Buloh, 47000 Selangor , Malaysia

4. Department of Anatomy, Universiti Teknologi MARA , Sungai Buloh, 47000 Selangor , Malaysia

Abstract

Abstract Humanised xenograft models and cancer cell lines are widely used for preclinical drug evaluation, biological studies, and targeted therapy strategies in cancer research. A humanised mouse model is a laboratory mouse that has been genetically modified to contain specific human genes, cells, or tissues. By introducing human-specific elements into rodents, researchers can create a more accurate representation of human physiological and pathological processes. Lacking an appropriate animal model for osteosarcoma (OS), hindered understanding of underlying mechanisms in OS metastasis progression. Markedly, metastasis influences the prognosis and treatment of osteosarcoma. Gaining insight into the mechanisms and occurrences of metastasis could potentially facilitate oncologists in improving therapies. Hence, it is important to develop a lung metastatic OS model to study the basic biology of its progression. This study has established a tumour-bearing mouse model using HOS-143B cell line which was injected into male NOD.SCID gamma (NSG) mice at two locations; intramuscularly (hind leg) and subcutaneously (back) respectively. The primary and metastatic tumour size was monitored by palpating the area of tumour induced and quantified using digital calliper. H&E staining was performed by pathologist to confirm metastasis. Our results showed that mice injected with 1 million cancer cells were unable to produce tumours. Meanwhile, mice injected with three million cancer cells showed tumour development and lung metastasis after 25 days of cancer cell inoculation. In conclusion, this study has successfully established a lung metastatic OS mouse model that could be useful for biological studies of OS. These findings imply that this model is essential for safety and efficacy before clinical trials, accelerate the translation from basic research to therapeutic applications.

Funder

Fundamental Research

Publisher

Oxford University Press (OUP)

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