Pancreatic neoplasms harbor different prognoses according to their histological typea benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP.

译文

胰腺肿瘤根据其浆液性囊腺瘤的组织学类型,良性,导管内乳头状黏液性肿瘤(IPMN)的低恶性潜能和导管腺癌(ADC)的高侵袭性,具有不同的预后。转化生长因子beta 1(TGF beta 1)可能调节肿瘤的生长。本研究分析并比较了IPMN中导管腺癌(n = 10)中其前体β1-潜伏期相关肽(β1-LAP),其潜在结合蛋白(LTBP)和其mRNA的表达。 8),浆液性囊腺瘤(n = 2)和正常组织(n = 5)。 LTBP被认为在潜在的TGFβ1及其在细胞外基质中的储备中的加工和主动分泌中起着战略作用。使用特异性抗体通过免疫组织化学评估β1-LAP和LTBP的定位,并通过逆转录酶聚合酶链反应分析评估TGFβ1 mRNA的表达。 β1-LAP在正常标本中仅少量表达,而未检测到LTBP。在10例ADC患者中,有9例在肿瘤细胞的细胞质中检测到了β1-LAP。在所有情况下,除了原位癌中的一种,在肿瘤腺周围的基质细胞中均存在强烈的染色。 LTBP仅在基质细胞和周围的细胞外基质中检测到。在具有轻度不典型增生的IPMN和膀胱腺瘤中,β1-LAP在上皮细胞中强烈表达,而在侵袭性IPMN中则检测不到。除侵袭性IPMN外(n = 2),基质细胞几乎没有被β1-LAP染色。在3例良性IPMN的肿瘤细胞和2例囊性腺瘤的2例肿瘤细胞中检测到LTBP,而基质未进行免疫染色。 TGFβ1mRNA在大多数肿瘤中强烈表达,并且在不同类型的肿瘤之间未观察到表达差异。在ADC和IPMN或膀胱腺瘤中,TGF beta 1的表达没有定量差异。但是,与导管ADC相比,后者能有效分泌TGFβ1,而肿瘤细胞既能表达β1-LAP又能表达LTBP。

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