Khamarudin Farhana, Muhamad Mudiana, Johari Ibahim Mohamad, Wan Mohamad Zain Wan Nor I'zzah, Aziz Mardiana Abdul, Adib Ridzuan Nurul Raudzah, Ab-Rahim Sharaniza
Department of Biochemistry and Molecular Medicine, Universiti Teknologi MARA, Sungai Buloh, 47000 Selangor, Malaysia.
Institute for Medical Molecular Biotechnology, Universiti Teknologi MARA, Sungai Buloh, 47000 Selangor, Malaysia.
Immunother Adv. 2024 Mar 23;4(1):ltae002. doi: 10.1093/immadv/ltae002. eCollection 2024.
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.
人源化异种移植模型和癌细胞系广泛应用于癌症研究中的临床前药物评估、生物学研究和靶向治疗策略。人源化小鼠模型是一种经过基因改造以包含特定人类基因、细胞或组织的实验室小鼠。通过将人类特异性元件引入啮齿动物,研究人员可以更准确地模拟人类生理和病理过程。由于缺乏合适的骨肉瘤(OS)动物模型,阻碍了对OS转移进展潜在机制的理解。值得注意的是,转移会影响骨肉瘤的预后和治疗。深入了解转移的机制和发生情况可能有助于肿瘤学家改进治疗方法。因此,开发一种肺转移OS模型来研究其进展的基本生物学特性很重要。本研究使用HOS-143B细胞系建立了荷瘤小鼠模型,将其分别注射到雄性NOD.SCID伽马(NSG)小鼠的两个部位:肌肉内(后腿)和皮下(背部)。通过触诊诱导肿瘤的区域监测原发性和转移性肿瘤大小,并使用数字卡尺进行量化。由病理学家进行苏木精-伊红(H&E)染色以确认转移。我们的结果表明,注射100万个癌细胞的小鼠无法产生肿瘤。同时,注射300万个癌细胞的小鼠在接种癌细胞25天后出现肿瘤发展和肺转移。总之,本研究成功建立了一种肺转移OS小鼠模型,可用于OS的生物学研究。这些发现意味着该模型对于临床试验前的安全性和有效性至关重要,可加速从基础研究到治疗应用的转化。