Koistinen Hannu, Seppälä Markku, Knuutila Sakari, Koistinen Riitta
Department of Clinical Chemistry, Helsinki University Central Hospital, Biomedicum Helsinki, PO Box 700, 00029 HUS, Finland.
Gynecol Oncol. 2006 Sep;102(3):546-51. doi: 10.1016/j.ygyno.2006.01.028. Epub 2006 Feb 23.
Extracellular matrix (ECM) components regulate growth and differentiation of epithelial cells, and impaired cell-ECM interaction may lead to increased cell proliferation and tumorigenesis. Whereas ECM has been shown to alter cellular morphology and reduce proliferation of HEC-1B endometrial adenocarcinoma cells, little is known about the underlying changes in gene expression. The purpose of this study was to investigate these changes.
We studied by cDNA array the effects of ECM components, as present in Matrigel basement membrane cell culture matrix, on gene expression in HEC-1B endometrial adenocarcinoma cells in respect of the same cells cultured on conventional plastic surface. Some of the changes were confirmed by protein analyses.
As expected, several growth-promoting genes were downregulated, while many genes associated with growth restriction were upregulated in Matrigel-grown carcinoma cells. Also, the expression of many 20S proteasome components was downregulated. The observed changes point to a less malignant phenotype of Matrigel-grown tumor cells, supported by reduced growth characteristics and morphology.
The study provides further insight into the mechanisms whereby ECM components may participate in the regulation of cell growth--by reducing expression of growth-promoting genes and increasing expression of the genes associated with growth restriction.
细胞外基质（ECM）成分调节上皮细胞的生长和分化，细胞与ECM相互作用受损可能导致细胞增殖增加和肿瘤发生。虽然已表明ECM可改变细胞形态并减少HEC - 1B子宫内膜腺癌细胞的增殖，但对基因表达的潜在变化知之甚少。本研究的目的是调查这些变化。
我们通过cDNA阵列研究了基质胶基底膜细胞培养基质中存在的ECM成分对HEC - 1B子宫内膜腺癌细胞基因表达的影响，并与在传统塑料表面培养的相同细胞进行了比较。部分变化通过蛋白质分析得到证实。
正如预期的那样，在基质胶中培养的癌细胞中，几个促进生长的基因被下调，而许多与生长限制相关的基因被上调。此外，许多20S蛋白酶体成分的表达也被下调。观察到的变化表明基质胶中培养的肿瘤细胞恶性表型较低，这一点得到生长特性和形态学改变的支持。
本研究进一步深入了解了ECM成分可能通过降低促进生长基因的表达和增加与生长限制相关基因的表达来参与细胞生长调节的机制。
