治癒癌症新解 防堵擴散是關鍵
摘錄自：天下雜誌 經濟學人電子報 2014/2/28
2014-02-18 Web
only 作者：經濟學人
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| 圖片來源：flickr.com/photos/urologysa/ |
擴散是癌症最陰險的一面。手術、放射線、藥物可以相當有效地處理原發性腫瘤，但只要腫瘤開始轉移、續發性腫瘤擴散至病人身體其他部份之時，這類療法的效果也會大大減低。因此，阻止轉移會是個重大成就；蓋氏整型外科研究中心的莫瑞提（Matteo Moretti）和麻省理工學院的卡姆（Roger Kamm）可能已經朝此目標前進了一步；他們創造的微實驗室晶片，可以模仿乳癌與骨髓之間的癌細胞轉移。
轉移的謎團之一就是，不同的原發性腫瘤傾向於轉移至不同的特定組織。兩位研究者為了測試他們裝置，研究了傾向轉移至骨髓的乳癌細胞，並利用裝置驗證一項假說，亦即此傾向源於骨髓信號分子CXCL5，以及乳癌細胞外膜上常見的分子受體CXCR2。
晶片本身有如2公分寬、以玻璃和塑膠做成的三明治，兩種材質之間有著相互連結的渠道，渠道內則填滿可以讓細胞生長的凝膠。莫瑞提博士和卡姆博士利用晶片矩陣模仿骨髓，並在每個晶片中央放人乳癌細胞；控制組則是以晶片矩陣模仿膠原蛋白。一如預期，癌細胞快速入侵骨髓，但沒有入侵膠原蛋白。問題在於，什麼東西吸引了癌細胞？
兩人為了找出答案，以培養CXCR2抗體的乳癌細胞再次進行實驗，結果發現那大幅減緩了癌細胞擴散。相反地，當他們在膠原蛋白陣列中加入CXCL5時，癌細胞便快速入侵。信號分子與分子受體間的連結，似乎就是骨頭吸引乳癌細胞的原因。
這是非常有用的資訊；以化學手段瞄準CXCR2受體，或是開發可以讓骨頭減少CXCL5分泌量的藥物，或許就能減緩、甚至停止乳癌轉移。不過，此晶片還有更廣泛的用途；莫瑞提博士和卡姆博士在開發晶片之時，還創造了可以測試多種細胞互動的方法，其他癌症與轉移組織間的互動亦包含在內。最終，那說不定可以減少轉移和續發性腫瘤，進而延長患者的壽命。（黃維德譯）
©The Economist
Newspaper Limited 2014
The Economist
Cancer
Secondary
goals
By The Economist
From The Economist
Published:
February 18, 2014
Feb 15th 2014 |
From the print edition
A better way to
understand metastasis.
THE most insidious
thing about cancer is its tendency to spread. A lone primary tumour can be
tackled by knife or radiation beam, as well as drugs, with a reasonable hope of
success. But once it has metastasised, and spread secondary cancers around a
patient's body, such treatments are much less likely to be effective for any
length of time. Stopping metastasis would thus be a great achievement. And a
device created by Matteo Moretti of the Galeazzi Orthopaedic Institute, in
Milan, and Roger Kamm of the Massachusetts Institute of Technology, may be a
step towards that goal. Their invention, which they describe in Biomaterials,
is a lab-on-a-chip that mimics the metastasis of breast cancer into bone
marrow.
One of the
mysteries of metastasis is why migrant cells from different sorts of primaries
prefer to set up home in particular types of secondary tissue. To test their
device the two researchers studied the well-established proclivity of
breast-cancer cells (pictured above) to colonise bone. They wanted to look at
the hypothesis that in this case the attraction is between a signalling molecule
called CXCL5, which bone cells use to talk to other cells, and a molecular
receptor called CXCR2, which is often found on the outer membranes of
breast-cancer cells.
The chip itself is
a glass and plastic sandwich 2cm across that contains a series of interlinked
channels in the junction between the two materials. The channels are filled
with a gel in which cells can grow. Dr Moretti, Dr Kamm and their students used
these chips to create matrices of blood vessels, bone cells and stem cells
which they hoped resembled the living marrow of a bone. They then placed
clusters of breast-cancer cells in the middle of each chip. As a control, they
did something similar using matrices of collagen (a protein abundant in bone)
instead of ersatz marrow. As they guessed would happen, the cancer cells
quickly invaded the marrow, but not the collagen. The question was, what was
attracting them in?
To find out, they
repeated the experiment with breast-cancer cells that had been incubated with
antibodies to CXCR2. These glom onto the receptors and reduce their attraction
to other substances. That slowed the cancer cells' spread down a lot. Conversely,
when they added CXCL5 to the collagen matrices, cancer cells moved in rapidly.
The link between messenger and receptor thus seems to be what makes bone so
attractive to breast-cancer cells.
This is useful
information. Taking chemical aim at the CXCR2 receptor, or developing drugs
that reduce the secretion by bone of CXCL5 might slow—or even
halt—breast-cancer metastasis. But the new chips have wider ramifications, too.
In making them Dr Moretti and Dr Kamm have created a way of testing many types
of cellular interaction, including those between other cancers and the tissues
they like to colonise. That may, eventually, result in less metastasis, fewer
secondaries and longer lives for patients.
©The Economist
Newspaper Limited 2014
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