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zoom RSS ガンの転移を準備する酵素の発見

<<   作成日時 : 2009/03/10 20:37   >>

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 ガンの転移を止める方法を発見したとする報告。
 ガンが原発巣から転移することがガンによる死亡の90%に関連するとされる。LOXという酵素が転移促進に重要であるとし、この酵素活動を抑える薬がガン転移を食い止める可能性がある。マウスの乳がんで研究されたが、この発見は他のタイプのがんにもあてはまると確信しているという。
 ガンがキャンプ地を設定するように体内の新たな場所を準備するためのシグナルを発する事でLOX (lysyl oxidase)は働く。この準備プロセスがないと新しい環境はガンが成長するために困難なものとなる。
 1つの重要な酵素が効果的にガンが転移することを可能にするのを引き起こしていると初めて同定された。
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Page last updated at 00:01 GMT, Sunday, 8 March 2009
Enzyme behind cancer spread found
http://news.bbc.co.uk/2/hi/health/7813072.stm

画像breast cancer
Breast cancer cells can spread to other parts of the body

Scientists say they have discovered a way to stop cancer spreading to other parts of the body.

Cancer metastasis, where the cancer spreads from its original location, is known to be responsible for 90% of cancer-related deaths.

Institute of Cancer Research scientists have found that an enzyme called LOX is crucial in promoting metastasis, Cancer Cell journal reports.

Drugs to block this enzyme's action could keep cancer at bay, they hope.

The researchers studied breast cancer in mice, but are confident that their findings will apply to humans with other cancer types too.

This new discovery provides real hope that we can develop a drug which will fight the spreading of cancer
Lead researcher Dr Janine Erler

LOX (lysyl oxidase) works by sending out signals to prepare a new area of the body for the cancer to set up a camp. Without this preparation process the new environment would be too hostile for the cancer to grow.

Lead researcher Dr Janine Erler described the discovery as "the crucial missing piece in the jigsaw that scientists have been searching for."

She said it was the first time one key enzyme has been identified as responsible for effectively allowing the cancer to spread.

"If we can interrupt the body's ability to prepare new locations for the cancer to spread to, we can effectively prevent cancer metastasis.

"Cancer metastasis is very difficult to treat and this new discovery provides real hope that we can develop a drug which will fight the spreading of cancer," she said.

Dr Julie Sharp, Cancer Research UK's science information manager, said: "A better understanding of how cancer spreads is crucial to improving the treatment of the disease. This research takes scientists a step closer to understanding this major problem - the next stage will be to find out if the LOX protein can be switched off to stop cancer spreading."

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Cancer Cell, Volume 15, Issue 1, 35-44, 6 January 2009
doi:10.1016/j.ccr.2008.11.012
Article

Hypoxia-Induced Lysyl Oxidase Is a Critical Mediator of Bone Marrow Cell Recruitment to Form the Premetastatic Niche

Janine T. Erler1,2,4,Kevin L. Bennewith1,3,4,Thomas R. Cox2,Georgina Lang2,Demelza Bird2,Albert Koong1,Quynh-Thu Le1andAmato J. Giaccia1,Go To Corresponding Author,

1 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
2 Section of Cell and Molecular Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK
3 Department of Medical Biophysics, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada
Corresponding author
4 These authors contributed equally to this work

Summary

Tumor cell metastasis is facilitated by premetastatic niches formed in destination organs by invading bone marrow-derived cells (BMDCs). Lysyl oxidase (LOX) is critical for premetastatic niche formation. LOX secreted by hypoxic breast tumor cells accumulates at premetastatic sites, crosslinks collagen IV in the basement membrane, and is essential for CD11b+ myeloid cell recruitment. CD11b+ cells adhere to crosslinked collagen IV and produce matrix metalloproteinase-2, which cleaves collagen, enhancing the invasion and recruitment of BMDCs and metastasizing tumor cells. LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. CD11b+ cells and LOX also colocalize in biopsies of human metastases. Our findings demonstrate a critical role for LOX in premetastatic niche formation and support targeting LOX for the treatment and prevention of metastatic disease.

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