生物谷報道：美國西北大學(xué)的科學(xué)家,，在先前的研究中意外發(fā)現(xiàn)，惡性黑色素瘤細(xì)胞里,，居然存在著一些也在干細(xì)胞中表現(xiàn)的蛋白質(zhì),，而且由于這些蛋白質(zhì)并不會在非惡性的腫瘤細(xì)胞，或是正常的細(xì)胞中出現(xiàn),，因此懷疑這些跟分裂復(fù)制能力高度相關(guān)的蛋白質(zhì),，是不是惡性黑色素瘤細(xì)胞蔓延極其兇惡的原因之一，最近在華盛頓特區(qū)所舉行的美國解剖學(xué)會研討會中,，同樣的由西北大學(xué)的研究團(tuán)隊,，提出最新的研究結(jié)果表示，研究人員利用干細(xì)胞生長發(fā)育的微環(huán)境條件,，成功的將原本兇惡的黑色素瘤細(xì)胞,，逆向的發(fā)育成為正常的皮膚細(xì)胞。  

    主導(dǎo)這個實驗計劃的  Mary  J.C.  Hendrix博士,，在四月二十九日的演講中表示,，就細(xì)胞的生理特征來說，干細(xì)胞和惡性腫瘤的細(xì)胞確實有很多相似的地方,。人體里的干細(xì)胞,，可以透過微環(huán)境中所傳遞而來的微量訊息，啟動不同的生理反應(yīng)機(jī)制,，分裂分化成為高達(dá)兩百多種不同的細(xì)胞,，而惡性腫瘤細(xì)胞，同樣的也利用存在的微環(huán)境,，釋出與接收調(diào)控生長分裂的訊號,，來主導(dǎo)細(xì)胞的代謝活動，因此若能利用誘導(dǎo)干細(xì)胞發(fā)育的想法,，確實有機(jī)會逆轉(zhuǎn)惡性腫瘤細(xì)胞的發(fā)育,，回復(fù)成為正常細(xì)胞的可能,。  

    結(jié)果研究人員發(fā)現(xiàn)當(dāng)惡性黑色素瘤細(xì)胞，會在斑馬魚胚胎干細(xì)胞發(fā)育的環(huán)境中,，居然釋出了一個稱為  Nodal的胚胎因子  (embryonic  factor),，就過去相關(guān)的研究資料顯示，  Nodal胚胎因子是干細(xì)胞之所以具有多能化  (pluripotency)的主要原因,，研究人員進(jìn)一步的阻斷  Nodal的分子活動,，使得原本分裂失控的惡性黑色素瘤細(xì)胞，回復(fù)成非常類似于正常皮膚的細(xì)胞,。  

    這一個新的突破,，結(jié)合了原本不相關(guān)的兩個研究領(lǐng)域，相關(guān)科學(xué)家認(rèn)為,，也許未來抑制腫瘤的研究,，加入了干細(xì)胞研究所掌握的知識，就可以輕易的突破了當(dāng)前治療的瓶頸,。

英文原文：

Reversing cancer cells to normal cells
A Northwestern University scientist describes new research that used an innovative experimental approach to provide unique insights into how scientists can change human metastatic melanoma cells back to normal-like skin cells -- by exposing the tumor cells to the embryonic microenvironment of human embryonic stem cells, the zebra fish and the chick embryo.
In earlier work, Northwestern University scientist Mary J.C. Hendrix and colleagues discovered that aggressive melanoma cells (but not normal skin cells nor less aggressive melanoma cells) contain specific proteins similar to those found in embryonic stem cells. This groundbreaking work led to the first molecular classification of malignant melanoma and may help to explain how, by becoming more like unspecialized stem cells, the aggressive melanoma cell gained enhanced abilities to migrate, invade and metastasize while virtually undetected by the immune system.

Now, in the American Association of Anatomists’ plenary lecture and symposium, at Experimental Biology 2007 in Washington, DC, Dr. Hendrix describes new research that used an innovative experimental approach to provide unique insights into how scientists can change human metastatic melanoma cells back to normal-like skin cells - by exposing the tumor cells to the embryonic microenvironment of human embryonic stem cells, the zebra fish and the chick embryo.

Dr. Hendrix’s plenary lecture on April 29 is a highlight of the scientific program of the American Association of Anatomists. Her presentation is titled "the convergence of embryonic and cancer signaling pathways: role in tumor cell plasticity." Plasticity refers to the ability of the tumor cell, like the embryonic cell, to express or change into multiple, different types of cells.

First, a quick primer on the shared characteristics of aggressive tumor cells and embryonic stem cells: Embryonic stem cells are pluripotent, meaning they are able to differentiate into any of the more than 200 cell types in the adult body. Which type of cell they become depends on the signals they receive from their microenvironment. Similarly, during cancer progression, malignant cells receive and release signals from their own microenvironment, cues that promote tumor growth and metastasis.

In order to better understand what signals the melanoma cells are sending and receiving, Dr. Hendrix and her colleagues used the microenvironment of the zebrafish to study whether the tumor cells could communicate with the zebrafish stem cells and affect their early development. The zebrafish is a widely-used organism for genetic and developmental studies because of its prolific reproduction, rapid development, and transparent embryo that develops outside the body (making it especially easy to simply watch development), and the fact it develops organs and tissues comparable to those in humans, such as heart, kidney, pancreas, bones and cartilage.)

Using the zebrafish model, and the extraordinary technologic advances made in microscopy and molecular biology in recent years, the team was able to show that the aggressive melanoma cells secrete Nodal, a critical component underling the two-way communication between tumor cells and the embryonic microenvironment. Nodal is an embryonic factor (also called a morphogen) responsible for maintaining the pluripotency of human embryonic stem cells: their ability to develop or "morph" into one of a variety of body cells. When aggressive melanoma and other tumor cells (recent findings also report Nodal expression in breast cancer and testicular cancer) regain the ability to express a potent embryonic morphogen like Nodal, the presence of the Nodal and the signals it sends and receives appear to play a key role in tumor cell plasticity and progression.

Most noteworthy, Dr. Hendrix’s team’s also has shown that inhibition of Nodal signaling leads to a reduction in melanoma cell invasiveness and ability to create new tumors. In fact, with inhibition of Nodal, the metastatic melanoma cells are reverted to a more benign skin cell without the ability to form tumors.

Findings from the zebrafish study were further confirmed in the human embryonic stem cell model and the chick embryo model - where inhibiting Nodal signaling led to the reversal of the melanoma cells to a more normal cell type.

This is a promising area of research, says Dr. Hendrix. The discovery of a new signalizing pathway in melanoma and other tumor cell types and the ability to inhibit Nodal and thus reverse the melanoma cell back toward a normal skin cell provide a previously unknown target for regulating tumor progression and metastasis.

Dr. Hendrix’s distinguished lecture is part of a session titled the cell microenvironment in development and cancer.

Source: Northwestern University