Droz D, Patey N, Paraf F, Chrétien Y, Gogusev J
Laboratoire de Pathologie Rénale, Hôpital Necker, Paris, France.
Lab Invest. 1994 Nov;71(5):710-8.
Cell to cell and cell to matrix interactions play a major role in tumor growth and invasion. Therefore, we studied the composition of extracellular matrices and the distribution of cell adhesion molecules in 50 renal cell tumors of various types and various grades of malignancy as compared with nontumoral kidney.
In the present study, we used immunolabeling with specific antibodies directed against the alpha 1, alpha 2, and alpha 3 chains of collagen type IV; laminin; heparan sulfate proteoglycan; fibronectin; collagen I; collagen III; the alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1, and beta 3 subunits of integrins; and ICAM-1, VCAM-1, and ELAM-1 molecules.
In clear cell type carcinomas (24 cases) the basal laminae surrounding the tumor islets contained the alpha 1 and alpha 2 chains of collagen type IV and heparan sulfate proteoglycan in all cases, and laminin in 96% of the cases. The alpha 3 chain of collagen IV was present in only one case, whereas fibronectin, collagen I, and collagen III were detected in nearly 50% of the cases. The tumor cells expressed alpha 3, alpha 6, and beta 1 integrin subunits in all cases, alpha 5 in 25%, alpha v beta 3 in 54%, and alpha 2 in none. ICAM-1 was detected in all cases, and VCAM-1 in 58%. The expression of the alpha 6 subunit was weak in 2 tumors of high grade, whereas the alpha v subunit was expressed in 7 of 14 low grade and in 7 of 10 intermediate and high grade tumors. In tubulopapillary carcinomas with chromophilic cells (12 cases), the most prominent findings were the presence of the alpha 3 chain of collagen IV in tumor basal laminae in 66% and the expression of the alpha 2 integrin subunit by the tumor cells in 58% of the cases, both features characterizing distal renal tubules. In chromophobic carcinomas (4 cases), the tumor basement membranes were tenuous and contained no fibronectin or interstitial collagens. The tumor cells expressed the alpha 6, alpha 2, alpha 3, beta 1, and alpha nu beta 3 integrin subunits but neither ICAM-1 nor VCAM-1 molecules. In oncocytomas (10 cases), the tumor basement membranes contained the alpha 1, alpha 2, and alpha 3 chains of collagen IV, laminin, and heparan sulfate proteoglycan. Fibronectin was not detected, whereas interstitial collagens were present in half of the cases. In all tumors, cells expressed the alpha 6 and beta 1 integrin subunits, whereas alpha 2, alpha 3, and alpha nu beta 3 were present in 30%, 60%, and 90% of the cases, respectively. ICAM-1 and VCAM-1 were not detected. The vascular endothelial cells of the stroma expressed the alpha 1, alpha 5, alpha 6, and beta 1 integrin subunits in all 50 of the studied tumors. In addition, ICAM-1 was detected in 84%, VCAM-1 in 50%, and ELAM-1 in 34% irrespective of tumor cell type, growth, or nuclear grade.
These results suggest that each type of renal cell tumor produces particular extracellular matrix components and expresses a characteristic repertoire of cell adhesion molecules, which could provide better understanding of the origin of these tumors. The expression of the alpha nu beta 3 integrin subunit was demonstrated in all types of renal cell tumors and was not found to be related to high grade tumors. Stromal vascular endothelial cells expressed activation molecules VCAM-1 and ELAM-1 in a significant number of cases in both benign and malignant tumors.
细胞间和细胞与基质间的相互作用在肿瘤生长和侵袭中起主要作用。因此，我们研究了50例不同类型和不同恶性程度的肾细胞肿瘤细胞外基质的组成以及细胞黏附分子的分布，并与非肿瘤性肾组织进行比较。
在本研究中，我们使用针对IV型胶原α1、α2和α3链；层粘连蛋白；硫酸乙酰肝素蛋白聚糖；纤连蛋白；I型胶原；III型胶原；整合素α1、α2、α3、α5、α6、αv、β1和β3亚基；以及细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和内皮白细胞黏附分子-1（ELAM-1）分子的特异性抗体进行免疫标记。
在透明细胞型癌（24例）中，肿瘤岛周围的基底膜在所有病例中均含有IV型胶原α1和α2链以及硫酸乙酰肝素蛋白聚糖，96%的病例含有层粘连蛋白。IV型胶原α3链仅在1例中出现，而近50%的病例中检测到纤连蛋白、I型胶原和III型胶原。肿瘤细胞在所有病例中均表达α3、α6和β1整合素亚基，25%表达α5，54%表达αvβ3，无一例表达α2。所有病例均检测到ICAM-1，58%检测到VCAM-1。在2例高分级肿瘤中α6亚基表达较弱，而在14例低分级肿瘤中的7例以及10例中高分级肿瘤中的7例中表达αv亚基。在嗜酸性细胞性管状乳头状癌（12例）中，最显著的发现是66%的肿瘤基底膜中存在IV型胶原α3链，58%的病例中肿瘤细胞表达α2整合素亚基，这两个特征均为远端肾小管的特征。在嫌色细胞癌（4例）中，肿瘤基底膜较薄，不含纤连蛋白或间质胶原。肿瘤细胞表达α6、α2、α3、β1和αvβ3整合素亚基，但未检测到ICAM-1和VCAM-1分子。在嗜酸细胞瘤（10例）中，肿瘤基底膜含有IV型胶原α1、α2和α3链、层粘连蛋白和硫酸乙酰肝素蛋白聚糖。未检测到纤连蛋白，半数病例存在间质胶原。在所有肿瘤中，细胞均表达α6和β1整合素亚基，而α2、α3和αvβ3分别在30%、60%和90%的病例中出现。未检测到ICAM-1和VCAM-1。在所有50例研究的肿瘤中，基质的血管内皮细胞均表达α1、α5、α6和β1整合素亚基。此外，无论肿瘤细胞类型、生长情况或核分级如何，84%检测到ICAM-1，50%检测到VCAM-1，34%检测到ELAM-1。
这些结果表明，每种类型的肾细胞肿瘤都会产生特定的细胞外基质成分并表达特定的细胞黏附分子谱，这有助于更好地理解这些肿瘤的起源。在所有类型的肾细胞肿瘤中均证实了αvβ3整合素亚基的表达，且发现其与高分级肿瘤无关。在良性和恶性肿瘤的大量病例中，基质血管内皮细胞均表达激活分子VCAM-1和ELAM-1。
