Rømer J, Pyke C, Lund L R, Ralfkiaer E, Danø K
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
J Invest Dermatol. 2001 Mar;116(3):353-8. doi: 10.1046/j.1523-1747.2001.01241.x.
In this study we have used in situ hybridization with radiolabeled antisense RNA probes to examine the expression of mRNA for urokinase-type plasminogen activator and its receptor in histologic samples of squamous cell (n = 7) and basal cell (n = 7) carcinomas of the skin. Messenger RNA for both urokinase-type plasminogen activator and its receptor were expressed in all of the squamous cell carcinomas, but could not be detected in the basal cell carcinomas. In all of the seven squamous cell carcinomas a signal for urokinase-type plasminogen activator receptor mRNA was detected focally in well-differentiated cancer cells surrounding keratinized pearls, and in four specimens urokinase-type plasminogen activator receptor mRNA was in addition expressed by cancer cells at the edge of invasively growing strands of tumor. Urokinase-type plasminogen activator mRNA expression was found in virtually all the cancer cells of the squamous cell carcinomas, and importantly we found, by hybridizations for urokinase-type plasminogen activator and its receptor mRNA on adjacent sections of squamous cell carcinomas, that it was exactly the invading cancer cells that simultaneously expressed both these components required for plasmin-mediated proteolysis at the cell surface. We have previously shown that both urokinase-type plasminogen activator and its receptor mRNA are expressed by the leading-edge keratinocytes in regenerating epidermis during mouse skin wound healing, and that wound healing is impaired in mice made deficient in plasminogen by targeted gene disruption. We propose that there are similarities between the mechanisms of generation and regulation of extracellular proteolysis during skin re-epithelialization and squamous cell carcinoma invasion. The ability of the squamous carcinoma cells to mimic the "invasive" phenotype of re-epithelializing keratinocytes may be one of the factors that make squamous cell carcinomas more aggressive tumors than basal cell carcinomas.
在本研究中，我们使用放射性标记的反义RNA探针进行原位杂交，以检测尿激酶型纤溶酶原激活剂及其受体的mRNA在皮肤鳞状细胞癌（n = 7）和基底细胞癌（n = 7）组织学样本中的表达。尿激酶型纤溶酶原激活剂及其受体的信使RNA在所有鳞状细胞癌中均有表达，但在基底细胞癌中未检测到。在所有7例鳞状细胞癌中，在角质化珠周围分化良好的癌细胞中局部检测到尿激酶型纤溶酶原激活剂受体mRNA信号，并且在4个标本中，侵袭性生长的肿瘤条索边缘的癌细胞也表达尿激酶型纤溶酶原激活剂受体mRNA。尿激酶型纤溶酶原激活剂mRNA表达几乎在鳞状细胞癌的所有癌细胞中均有发现，重要的是，我们通过在鳞状细胞癌相邻切片上对尿激酶型纤溶酶原激活剂及其受体mRNA进行杂交发现，正是侵袭性癌细胞同时表达了细胞表面纤溶酶介导的蛋白水解所需的这两种成分。我们先前已经表明，在小鼠皮肤伤口愈合过程中，尿激酶型纤溶酶原激活剂及其受体mRNA在再生表皮的前沿角质形成细胞中表达，并且通过靶向基因破坏使纤溶酶原缺乏的小鼠伤口愈合受损。我们提出，在皮肤再上皮化和鳞状细胞癌侵袭过程中，细胞外蛋白水解的产生和调节机制之间存在相似性。鳞状癌细胞模拟再上皮化角质形成细胞“侵袭性”表型的能力可能是使鳞状细胞癌比基底细胞癌更具侵袭性肿瘤的因素之一。
