佛羅里達州梅奧診所的研究人員已經(jīng)確定促發(fā)最常見的肺癌類型和其致命性轉移的單個基因。他們的研究表明這種基因--基質(zhì)金屬蛋白酶10（MMP-10）也驅(qū)動其他形式的癌癥。
研究結果發(fā)表在期刊PLoS ONE上,，這項研究表明MMP-10是一種生長因子的分泌，然后腫瘤樣干細胞樣細胞利用MMP-10來保持自己的重要,。然后這些細胞驅(qū)使肺癌的發(fā)生及其擴散轉移,。
研究結果提出重燃了治療非小細胞肺癌的希望，非小細胞肺癌美國癌癥死亡的首要原因,。研究人員發(fā)現(xiàn)通過關閉MMP-10,，肺癌干細胞失去發(fā)展成腫瘤的能力。當肺癌干細胞重新表達該基因時,，它們可以再次形成腫瘤,。
佛羅里達州梅奧診所癌癥生物學部教授Alan Fields博士表示：我們的研究數(shù)據(jù)提供的證據(jù)表明：MMP-10在癌癥中起著雙重作用。它不但刺激腫瘤干細胞的生長,，同時也刺激腫瘤細胞的轉移潛能,。
腫瘤干細胞表達MMP-10，并用它促進自己的生長,。已知的基質(zhì)金屬蛋白酶基因成員在腫瘤微環(huán)境,、腫瘤周圍的細胞和組織中大多數(shù)會表達。這些基因產(chǎn)生的酶參與癌細胞擴散過程,。事實上,，像MMP-10基因編碼基質(zhì)金屬蛋白酶，實際上是對腫瘤干細胞的生長和腫瘤干細胞的維持是必需的,。研究人員也驚奇地發(fā)現(xiàn)腫瘤干細胞比其余大部分腫瘤細胞能產(chǎn)生更多的MMP-10,。
研究人員說，他們的研究表明MMP-10的過度表達也可能對其他人類腫瘤干細胞的生存至關重要,。他們觀察到MMP-10的表達與人類大腸癌,、黑色素瘤、乳腺癌,、腎,、前列腺癌干細胞樣細胞轉移行為之間有聯(lián)系。
研究人員正在尋找MMP-10刺激腫瘤干細胞生長的機制，并正在設計可以用來抑制MMP-10活性的抑制劑,。
Fields博士表示：鑒于其在腫瘤干細胞和轉移中雙重作用,，靶向MMP-10可能有效地治療這些腫瘤。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0035040
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Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential
Verline Justilien#, Roderick P. Regala#, I-Chu Tseng, Michael P. Walsh, Jyotica Batra, Evette S. Radisky, Nicole R. Murray, Alan P. Fields*
Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10−/− mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells.
