PDF Version for Printing
The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.
View the Table of Contents for the May 15 issue of Cancer Research.
Chabottaux et al. Page 5165
Although membrane-type 4 matrix metalloproteinase (MT4-MMP) was originally isolated from a human breast carcinoma, its implication during breast cancer progression is unknown. For the first time, Chabottaux et al. provide evidence by immunohistochemistry of higher MT4-MMP production by epithelial cancer cells in human breast carcinoma samples. They demonstrate that the over-expression of MT4-MMP in the human breast cancer MDA-MB231 cell line promotes primary tumor growth leading to increased lung metastases. They identify, in this way, MT4-MMP as a new target to design anticancer strategies.
Jost et al. Page 5234
In contrast to most matrix metalloproteinases (MMPs), MMP-19 is expressed in normal human epidermis and is down-regulated during malignant transformation. To explore the unknown in vivo functions of MMP-19, Jost et al. applied different in vivo models of angiogenesis into mutant mice lacking Mmp-19. Increased early angiogenic response and increased tumor invasion were observed in Mmp-19–/– mice. Therefore, in contrast to most MMPs which promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP in order to improve anticancer strategies.
Page 5387
The efficacy of treating Ph-positive acute lymphoblastic leukemia (ALL) with the tyrosine kinase inhibitor Imatinib is limited. Mishra et al. treated murine Bcr/Abl P190 leukemic cells with 5 µM Imatinib in the absence and presence of stroma. Although a high percentage of the cells in both types of cultures were killed, residual cells in the stromal cocultures started to reproliferate after 6 days. The drug-resistant cells expressed Bcr/Abl protein that was still inhibited by Imatinib and may represent a subpopulation less dependent upon Bcr/Abl for survival. Elimination of this subpopulation may improve treatment of Ph-positive ALL.
Page 5504
Cyclooxygenase-2 (COX-2) is overexpressed in about 40% of human breast cancers and correlates with HER-2/neu expression. A functional relationship between COX enzymes and estrogen biosynthesis has been suggested. COX-derived prostaglandins increase aromatase transcription in vitro, and COX and aromatase are coordinately expressed in human breast cancers. Subbaramaiah et al. directly demonstrate a causal relationship between COX expression and aromatase activity both in vivo and in vitro by genetically manipulating COX-2 levels. Furthermore, this study identifies a novel correlation between HER-2/neu overexpression and aromatase activity in human breast cancers, and demonstrates that HER-2/neu–mediated induction of aromatase activity is suppressed by inhibiting COX-2. Thus, this study provides the first demonstration of a functional relationship between HER-2/neu, COX-2, and aromatase activity, and identifies HER-2/neu as a novel determinant of aromatase activity in human breast cancer.