Rubio C A
Gastrointestinal and Liver Pathology Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
Anticancer Res. 2006 May-Jun;26(3B):2275-8.
Dilated neoplastic glands, some with a layer of flat tumour cells and others lacking a group of consecutive lining tumour cells (i.e., glandular gaps called pores), were previously found at the leading invading tumour edge of colorectal carcinomas. Through the glandular pores, the retained intraglandular material was siphoned off directly into the juxtaposed extracellular matrix (ECM). The tumour cell fabricates, rich in proteolytic enzymes, disrupted the paratumoral anatomy of the ECM and encouraged further tumour penetration. In this work, cell proliferation in the neoplastic glands of the outermost advancing front of seven colonic carcinomas was studied with the proliferation marker Ki67. A total of 105 neoplastic glands were investigated in the seven tumours. In 33 of the 35 neoplastic glands with flat tumour cells, no Ki67 expression could be recorded in the flat cells. In the other two neoplastic glands, only occasional flat tumour cells showed Ki67 expression. The remaining (non-flat) neoplastic cells in the lateral and proximal aspects in the same 35 glands showed Ki67 expression. In 19 out of the 35 neoplastic glands with pores, the tumour cells at the tip of the pores (non-flat) showed Ki67 expression. In the remaining 16 neoplastic glands with pores, the tumour cells at the tip of the pores showed no Ki67 expression. In 15 out of the 35 neoplastic complete glands (i.e., having neither flat tumour cells nor epithelial pores) variable amounts of tumour cells lacking Ki67 expression were seen at the leading invading front. In the remaining 20 complete glands, all tumour cells showed Ki67 expression at the leading invading front. These preliminary results showed, for the first time, that human colonic flat neoplastic cells arrest their proliferation at the invading tumour front. The possibility that these Ki67-negative tumour cells were arrested in G1-phase was entertained. It is not inconceivable that this unexpected paradoxical biological behaviour of flat tumour cells might be connected with the formation of glandular pores at the level of advancing invasion in colonic carcinomas.
先前在结直肠癌侵袭前沿发现扩张的肿瘤性腺管，有些腺管有一层扁平肿瘤细胞，而另一些则缺乏连续的一层内衬肿瘤细胞（即称为孔隙的腺管间隙）。通过腺管孔隙，潴留的腺管内物质被直接虹吸到相邻的细胞外基质（ECM）中。富含蛋白水解酶的肿瘤细胞破坏了ECM的肿瘤旁解剖结构，并促进肿瘤进一步浸润。在这项研究中，用增殖标志物Ki67研究了7例结肠癌最外层推进前沿肿瘤性腺管中的细胞增殖情况。在这7个肿瘤中，共研究了105个肿瘤性腺管。在35个有扁平肿瘤细胞的肿瘤性腺管中，33个扁平细胞中未检测到Ki67表达。在另外2个肿瘤性腺管中，仅偶尔有扁平肿瘤细胞显示Ki67表达。在同一35个腺管的外侧和近端的其余（非扁平）肿瘤细胞显示Ki67表达。在35个有孔隙的肿瘤性腺管中，19个孔隙顶端的肿瘤细胞（非扁平）显示Ki67表达。在其余16个有孔隙的肿瘤性腺管中，孔隙顶端的肿瘤细胞未显示Ki67表达。在35个完整肿瘤性腺管（即既无扁平肿瘤细胞也无上皮孔隙）中，15个在侵袭前沿可见不同数量缺乏Ki67表达的肿瘤细胞。在其余20个完整腺管中，所有肿瘤细胞在侵袭前沿均显示Ki67表达。这些初步结果首次表明，人结肠扁平肿瘤细胞在肿瘤侵袭前沿停止增殖。有人认为这些Ki67阴性肿瘤细胞可能停滞在G1期。扁平肿瘤细胞这种意外的矛盾生物学行为可能与结肠癌侵袭进展水平上腺管孔隙的形成有关，这并非不可想象。
