Plxdc1, also known as Tumor endothelial marker 7 (TEM7), has been associated with multiple biological functions. It was initially identified as a gene highly expressed in glioblastoma endothelial cells [5]. Functionally, it has been implicated in angiogenesis, and PLXDC1 and PLXDC2 were identified as transmembrane receptors for the multifunctional factor PEDF [6].

In cancer, PLXDC1 shows significant implications. In pancreatic ductal adenocarcinoma, PLXDC1+ tumor-associated pancreatic stellate cells promote a desmoplastic and immunosuppressive niche, contributing to CD8 T cell exhaustion and poor immunotherapy efficacy [1]. In gastric cancer, its overexpression is associated with poor prognosis and immune evasion, and it can be an independent biomarker [2]. In colon cancer, high expression of PLXDC1 is related to cancer stages and nodal metastasis, and targeting it inhibits cancer cell viability, invasion, and macrophage polarization towards the M2 phenotype via the IL-6/STAT3 pathway [3]. In glioblastoma, bevacizumab-induced infiltrative growth is driven by vascular endothelium and depends on PLXDC1 activation of tumor cells [4]. In resectable gastric cancer, TEM7 (PLXDC1) promotes cancer cell migration and invasion, and its expression is closely related to the clinical outcome of patients [7].

In conclusion, Plxdc1 plays crucial roles in angiogenesis and cancer-related processes such as tumor growth, metastasis, and immune evasion. The studies, though not specifically from KO/CKO mouse models in the provided references, have significantly contributed to understanding its functions in disease, particularly in various cancer types. This knowledge may provide potential therapeutic targets for anti-angiogenesis and cancer treatment.