Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI–transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics.
由于癌细胞增殖对叶酸（FA）的高需求，大多数癌症中检测到叶酸受体1（FR1）的显著过表达。据我们所知，目前尚未有研究详细描述前列腺癌（PCa）中FR1的表达特征及其调控机制在治疗与诊断可行性方面的表现。本研究通过Western blot、qRT-PCR和免疫荧光技术对细胞培养物及组织切片进行分析。此外，我们利用FA功能化脂质复合物来评估FR1靶向递送进入PCa细胞的潜力。值得注意的是，我们在健康前列腺上皮细胞及健康前列腺组织中检测到高水平的FR1-mRNA。然而，我们通过实验证明，体外培养的PCa细胞及PCa组织显示出显著增强的FR1膜定位，使受体最终得以发挥功能。通过图像分析，我们将这些变化与糖基磷脂酰肌醇转酰胺酶（GPI-T）的过表达相关联。体外PCa细胞及PCa组织中GPI-T呈现最强的过表达，从而诱导FR1膜定位。最后，我们利用FA功能化脂质复合物选择性将pDNA转染至PCa细胞，并证实了FR1的治疗潜力。因此，FR1是PCa靶向治疗传递途径中极具前景的候选靶点，结合GPI-T检测，可在现有诊断方法基础上提供预测性影像学评估。
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