mProX™ Human SIRPA Stable Cell Line

Zhou, Zhicheng et al. "Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma." Cancer cell vol. 40,11 (2022): 1324-1340.e8.
Checkpoint inhibition immunotherapy has transformed cancer care, though resistance remains a challenge. This study conducted comprehensive transcriptomic and proteomic analyses across various melanoma clinical cohorts undergoing anti-PD-1 treatment, examining both bulk and single-cell levels. Surprisingly, it unveiled an unexpected role of tumor-intrinsic SIRPA, traditionally seen as a major immune inhibitor in macrophages, in enhancing antitumor immunity. The loss of SIRPA expression signaled melanoma dedifferentiation, linked to immunotherapy effectiveness. Inhibiting SIRPA in melanoma cells impeded CD8+ T cell-mediated tumor eradication, and mice with SIRPA-deficient melanoma tumors showed no response to anti-PD-L1 treatment. Conversely, melanoma-specific SIRPA overexpression significantly improved immunotherapy response, with regulation tied to its pseudogene, SIRPAP1. These findings underscore SIRPA's complex role in the tumor ecosystem, revealing cell-type-specific opposing effects on immunotherapy outcomes.
Zhou, Zhicheng et al. "Tumor-intrinsic SIRPA promotes sensitivity to checkpoint inhibition immunotherapy in melanoma." Cancer cell vol. 40,11 (2022): 1324-1340.e8.
Pubmed: 36332624   DOI: 10.1016/j.ccell.2022.10.012

Wang, Peng. et al. "SIRPA enhances osteosarcoma metastasis by stabilizing SP1 and promoting SLC7A3-mediated arginine uptake." Cancer letters, 2023.
The function of signal regulatory protein alpha (SIRPA) has been extensively examined in macrophages and dendritic cells, but its role in tumors remains relatively understudied. Notably, recent research has shown that SIRPA is overexpressed in osteosarcoma tissues, particularly in metastatic tissues, and is correlated with poor clinical outcomes. Studies have revealed that knockdown of SIRPA in osteosarcoma cells decreases their migration capacity by decreasing the stability of specificity protein 1 (SP1) and the uptake of arginine. Furthermore, it has been found that SIRPA phosphorylates SP1 at threonine 278 (Thr278) through activation of extracellular signal-regulated kinase (ERK), protecting SP1 from degradation. SP1, in turn, enhances the expression of solute carrier family 7 member 3 (SLC7A3) by binding to its promoter and increasing the uptake of arginine, promoting osteosarcoma cell migration. Interestingly, it has been discovered that arginine can also stabilize SP1 independently of ERK, forming a self-reinforcing "SP1 stabilization circle." However, this circle can be disrupted by combined treatment with an anti-SIRPA antibody and arginase, leading to impaired tumor metastasis in mice with xenografts formed from SIRPA-overexpressing cells. In conclusion, this research demonstrates that SIRPA upregulation contributes to osteosarcoma metastasis through the "SP1 stabilization circle" and SLC7A3-mediated arginine uptake, making it a potential target for osteosarcoma treatment.
Wang, Peng. et al. "SIRPA enhances osteosarcoma metastasis by stabilizing SP1 and promoting SLC7A3-mediated arginine uptake." Cancer letters, 2023.
Pubmed: 37769797   DOI: 10.1016/j.canlet.2023.216412