Pancreatic ductal adenocarcinoma (PDAC) stands as a highly aggressive and lethal cancer, characterized by a grim prognosis and scarce treatment alternatives. Within this context, TRPV6, a calcium-permeable channel, emerges as a noteworthy candidate due to its overexpression in various cancers, capable of influencing the cell behavior in different cancer entities. Nonetheless, the exact expression pattern and functional significance of TRPV6 in the context of PDAC remains enigmatic. This study scrutinizes the expression of TRPV6 in tissue specimens obtained from 46 PDAC patients across distinct stages and grades. We manipulated TRPV6 expression (knockdown, overexpression) in the human PDAC cell lines Panc-1 and Capan-1. Subsequently, we analyzed its impact on multiple facets, encompassing Ca2+influx, proliferation, apoptosis, migration, chemoresistance, and tumor growth, both in vitro and in vivo. Notably, the data indicate a direct correlation between TRPV6 expression levels, tumor stage, and grade, establishing a link between TRPV6 and PDAC proliferation in tissue samples. Decreasing TRPV6 expression via knockdown hampered Ca2+influx, resulting in diminished proliferation and viability in both cell lines, and cell cycle progression in Panc-1. The knockdown simultaneously led to an increase in apoptotic rates and increased the susceptibility of cells to 5-FU and gemcitabine treatments. Moreover, it accelerated migration and promoted collective movement among Panc-1 cells. Conversely, TRPV6 overexpression yielded opposing outcomes in terms of proliferation in Panc-1 and Capan-1, and the migration of Panc-1 cells. Intriguingly, both TRPV6 knockdown and overexpression diminished the process of tumor formation in vivo. This intricate interplay suggests that PDAC aggressiveness relies on a fine-tuned TRPV6 expression, raising its profile as a putative therapeutic target.
胰腺导管腺癌（PDAC）是一种高度侵袭性且致命的癌症，其特点是预后不良且治疗选择有限。在此背景下，钙离子通道TRPV6因其在多种癌症中的过度表达并能够影响不同癌症实体的细胞行为而成为一个值得关注的候选分子。然而，TRPV6在PDAC中的确切表达模式及功能意义仍不明确。本研究检测了46例不同分期和分级的PDAC患者组织样本中TRPV6的表达情况。我们在人PDAC细胞系Panc-1和Capan-1中调控了TRPV6的表达（敲低、过表达），随后分析了其对钙离子内流、增殖、凋亡、迁移、化疗耐药性及体内外肿瘤生长等多方面的影响。值得注意的是，数据显示TRPV6表达水平与肿瘤分期和分级呈正相关，并在组织样本中建立了TRPV6与PDAC增殖之间的联系。通过敲低TRPV6表达可抑制钙离子内流，导致两种细胞系的增殖和活力下降，并阻滞Panc-1细胞的细胞周期进程。敲低同时导致细胞凋亡率增加，并增强细胞对5-氟尿嘧啶和吉西他滨治疗的敏感性。此外，它还加速了Panc-1细胞的迁移并促进其集体运动。相反，TRPV6过表达在Panc-1和Capan-1的增殖以及Panc-1细胞的迁移方面产生了相反的效果。有趣的是，无论是TRPV6敲低还是过表达，均减弱了体内肿瘤形成的过程。这种复杂的相互作用表明，PDAC的侵袭性依赖于精细调控的TRPV6表达，从而提升了其作为潜在治疗靶点的价值。
肿瘤(癌症)患者之家