The role of KIF9 in glioma invasion

描述（由申请人提供）：恶性胶质瘤的一个关键作用是肿瘤细胞侵入大脑的局部正常区域。由于手术切除足够的边缘以捕获这些侵袭性细胞的局限性，胶质瘤在治疗后很可能复发。更好地了解胶质瘤细胞侵袭的机制可能有助于更有效地治疗胶质瘤。小胶质细胞可以增强胶质瘤的侵袭，胶质瘤中这些髓样细胞的水平越高，预后越差。因此，更好地了解小胶质细胞刺激胶质瘤侵袭的机制可以为治疗提供新的机会。这个提议将解决潜在的作用

DESCRIPTION (provided by applicant): A critical role in glioma malignancy is played by invasion of the tumor cells into local, normal regions of the brain. Because of the limitations on surgery to remove adequate margins to capture these invasive cells, glioma is highly likely to recur after treatment. A better understanding of the mechanisms by which glioma cells invade may enable more effective treatment of glioma. Microglia can enhance glioma invasion, and higher levels of these myeloid cells in gliomas correlates with worse prognosis. A better understanding the mechanisms by which microglia can stimulate glioma invasion could therefore provide new opportunities for treatment. This proposal will address the potential role of the product of the KIF9 gene in microglial stimulation of glioma invasion. The KIF9 gene encodes a kinesin family member and overexpression of KIF9 in gliomas is correlated with shorter survival. Kinesins are associated with movement of cellular components along microtubules. In preliminary studies, we find that suppression of KIF9 reduces microglia-stimulated glioma invasion and secretion of proteases associated with matrix degradation. We therefore hypothesize that KIF9 contributes to glioma invasion through enabling the trafficking of matrix proteolytic enzymes to the plasma membrane for secretion, resulting in enhanced invasive capabilities. The role of KIF9 in invasion will be tested in two specific aims. In Aim 1, we will evaluate the importance of KIF9 for microglia-stimulated glioma invasion in vitro. In Aim 2, we will use intracranial injection to test the importance of KIF9 for invasion in vivo. If successful, this grant will establish the value of KIF9 as a potential new target for the development of novel therapeutics.