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Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma

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Page 2164–71

The incidence and mortality of head and neck squamous cell carcinoma (HNSCC) has been increasing, with current 5-year survival rates of less than 50%. Hepatocyte growth factor (HGF) is a multifunctional growth factor that contributes to the carcinogenesis and progression of HNSCC. MET is a specific receptor tyrosine kinase for hepatocyte growth factor that is upregulated in HNSCC and whose signal transduction induces genes involved in the progressive and invasive characteristics of HNSCC. To elucidate how HGF affects downstream functional gene expression, Susuki and colleagues examined the expression of microRNA (miRNA) before and after HGF stimulation in HNSCC cells. MiRNA are non-coding small RNA that regulate cellular proliferation and function by interfering in the translation of target mRNA. Recent studies have shown that altered expression of several miRNA induces various human malignancies. Focusing on miR-200c and miR-27, the researchers found downregulation of both of these miRNA following HGF stimulation. The researchers suggest that altered expression of miRNA regulated by HGF might contribute to HNSCC progression and invasion.

doi: 10.1111/j.1349-7006.2011.02096.x

Semi-quantitative evaluation of CD44+/CD24 tumor cell distribution in breast cancer tissue by a newly developed fluorescence immunohistochemical staining method

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Page 2132–38

Recurrent cases of breast cancer are often resistant to conventional treatment, possibly due in part to chemoresistant cancer stem cells. CD44+/CD24 tumor cells are one putative type of breast cancer stem cell and have been reported to be associated with invasion and metastatic ability in breast cancer. Kai and colleagues previously confirmed the chemoresistance of CD44+/CD24 tumor cells from the breast cancer cell line MCF-7. The researchers then sought to develop an immunofluorescence method to quantitatively analyze CD44+/CD24 tumor cell distribution in breast cancer tissue to help better define the role of CD44+/CD24 tumor cells in breast cancer. Improved triple staining immunohistofluorescence and a simulated laser capture microdissection method was used to distinguish CD44+/CD24 tumor cells at a single cell level. With this method, the researchers examined the relationships between CD44+/CD24 cell population size, chemoresistance and lymph node metastasis. CD44+/CD24 tumor cell distribution was heterogenous in breast cancer tissue and lymph node metastasis. Using a xenograft mouse model, the researchers found that the hedgehog signaling inhibitor cyclopamine repressed the tumorigenicity of CD44+/CD24 cells. The authors suggest that their semi-quantitative immunohistochemical analysis is valuable for identifying a small population of cells in cancer tissues and that the hedgehog signaling pathway inhibitors, including cyclopamine, might be useful for the therapeutic targeting of CD44+/CD24 tumor cells in breast cancer.

doi: 10.1111/j.1349-7006.2011.02063.x

Asbestos surface provides a niche for oxidative modification

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Page 2118–25

Respiratory exposure to asbestos, a natural fibrous mineral heavily used in industry in the last century, results in a high risk of malignant mesothelioma and lung cancer. Due to its long incubation period, many countries expect increased incidence of mesothelioma in the coming decades. Although the mechanism of asbestos-induced carcinogenesis remains largely unknown, the high capacity of asbestos to adsorb and accommodate biomolecules on its surface has been associated with cellular and genetic toxicity. Nagai and colleagues used matrix-assisted laser desorption ionization-time of flight mass spectrometry to identify and classify proteins from lysates that adsorb to the surface of commercially used asbestos. The results demonstrate that crocidolite, amosite and chrysotile, three types of asbestos, adsorb DNA and specific proteins, thereby providing a niche for oxidative modification via catalytic iron. Among the proteins identified to interact with asbestos were hemoglobin and chromatin constituents such as DNA and histones, which the authors suggest might be particularly important. The authors suggest a novel hypothetical mechanism for asbestos-induced carcinogenesis involving genetic alterations.

doi: 10.1111/j.1349-7006.2011.02087.x