胰腺癌是一個幾乎沒有治療的惡性腫瘤，得了胰腺癌等于判死刑，一半病人會六個月內(nèi)死去，故稱之為“癌癥之王”。 胰腺位于腹腔深部位置和胰腺癌癥狀不明顯，常規(guī)的影像學檢查很難發(fā)現(xiàn)早期胰腺癌，因此早期發(fā)現(xiàn)或診斷胰腺癌很難。這種腫瘤進展兇猛、致死性極強、對大部分化療藥物治療敏感，而且手術(shù)切除率低。當胰腺癌被發(fā)現(xiàn)時，大部分病人腫瘤已經(jīng)到中晚期。
胰腺癌有非常厚的“堡壘”，即大量的細胞外間質(zhì)和極度貧乏的血管，但胰腺癌具有超強的營養(yǎng)物質(zhì)獲取能力。賽音賀西格老師與中山醫(yī)院樓文輝教授合作，通過七年的不懈努力，建立了高分辨率的3D重建腫瘤內(nèi)部結(jié)構(gòu)染色方法。通過這種方法揭開了胰腺癌的神秘物質(zhì)運輸通道的面紗-發(fā)現(xiàn)一種新型的“毛毛”微血管。這些微血管的細胞的背面長出巨大的突起，使微血管血管變成一個大量突起的類似巨型“毛毛蟲”的怪物。
臨床標本的數(shù)據(jù)分析結(jié)果顯示血管內(nèi)皮細胞基底面微絨毛可能大大提高了微血管的糖運輸能力。他們把這個新發(fā)現(xiàn)的內(nèi)皮細胞突起命名為“Basal microvilli "-內(nèi)皮細胞基底微絨毛 "，并把這個發(fā)現(xiàn)發(fā)表在國際頂尖病理學雜志“The Journal of pathology "，美國北卡大學的Andrew C. Dudley and Victoria L. Bautch博士同期發(fā)表了“Feeding cancer’s sweet tooth: specialized tumor vasculature shuttles glucose in Pancreatic ductal adenocarcinoma”-“喂腫瘤的糖牙-胰腺導(dǎo)管癌內(nèi)糖運輸?shù)难芸燔?rdquo;評論文章。這些細胞突起深入到胰腺癌組織的發(fā)達的間質(zhì)中，甚至可以延伸到腫瘤細胞周圍或腫瘤細胞之間。如同小腸微絨毛，血管內(nèi)皮細胞基底面微絨毛大大增加了微血管內(nèi)皮細胞的交換面積和物質(zhì)交換深度，從而極少微血管可以滿足胰腺癌細胞旺盛的代謝需求。
雖然體內(nèi)有些細胞，例如骨細胞，星型膠質(zhì)細胞等，通過細胞突起獲得能量物質(zhì)，但在極性的上皮細胞當中一般不存在基底面具有物質(zhì)交換功能突起，這是首次觀察到血管內(nèi)皮基底面存在大量具有物質(zhì)交換功能的突起。這種特殊的細胞突起只有在腫瘤內(nèi)存在，這點可能是胰腺癌的致命弱點-“Achilles heels”。
利用這個胰腺癌特異的途徑輸送治療藥物或者通過靶向分子抑制或破壞此結(jié)構(gòu)，可能將成為治療胰腺癌的或首選途徑。此項工作得到余龍教授和很多國內(nèi)外同行大力支持。
原文鏈接：Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET–CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours. |
