Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis
Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis
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DOI：
10.1097/01.pas.0000172192.25295.45
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发表时间：
2005-10-01
影响因子：
5.6
通讯作者：
Suda, K
中科院分区：
文献类型：
--
作者：
Kumasaka, T;Seyama, K;Suda, K
淋巴管肌瘤病(LAM)仅影响育龄妇女，累及肺部和中轴淋巴系统，常合并肾血管肌脂肪瘤。LAM病变是由LAM细胞的增殖和结节硬化症复合体(TSC)基因之一的突变引起的。最近的研究表明，LAM细胞可以迁移或转移，在多个器官形成新的病变，尽管它们表现出形态上的良性外观。在先前的研究中，我们报道了LAM相关的淋巴管生成及其在LAM进展中的作用。在本研究中，我们进一步关注LAM的淋巴异常：LAM相关的乳糜液(5例胸腔积液，2例腹水)，手术切除的横隔部(1例)，以及包括胸管、不同区域的淋巴结和横隔部淋巴系统在内的轴状淋巴系统(5例尸检)。我们证明在所有被检查的乳糜液中，LAM细胞团被淋巴管内皮细胞(LCC)包裹。我们发现LAM病变位于横隔部(2/5例尸检和1例手术标本)、胸导管(5/5例)和淋巴结(腹膜后(5例)、纵隔(4例/5例)、左静脉角(5例/5例)，总阳性率为68%~88%，但在远离中轴淋巴干(颈部[1/5]和腋窝[0/5])的远处淋巴结较少或没有。LCC存在于LAM内淋巴管中，LAM细胞沿淋巴系统增殖。在体外培养体系中，LCC可碎裂为每个增殖的LAM细胞。这些发现提示LAM相关的淋巴管生成将LAM病变划分为束状或束状结构，最终将LCC送入淋巴循环，LCC在LAM病变的扩散中起中心作用。
Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphologically benign appearance. In the previous study, we reported LAM-associated lymphangiogenesis and implicated its role in the progression of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lymphatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retroperitoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical [1 of 5] and axillary [0 of 5]). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.