生物谷报道:美国西北大学的科学家,在先前的研究中意外发现,恶性黑色素瘤细胞里,居然存在着一些也在干细胞中表现的蛋白质,而且由于这些蛋白质并不会在非恶性的肿瘤细胞,或是正常的细胞中出现,因此怀疑这些跟分裂复制能力高度相关的蛋白质,是不是恶性黑色素瘤细胞蔓延极其凶恶的原因之一,最近在华盛顿特区所举行的美国解剖学会研讨会中,同样的由西北大学的研究团队,提出最新的研究结果表示,研究人员利用干细胞生长发育的微环境条件,成功的将原本凶恶的黑色素瘤细胞,逆向的发育成为正常的皮肤细胞。
主导这个实验计划的 Mary J.C. Hendrix博士,在四月二十九日的演讲中表示,就细胞的生理特征来说,干细胞和恶性肿瘤的细胞确实有很多相似的地方。人体里的干细胞,可以透过微环境中所传递而来的微量讯息,启动不同的生理反应机制,分裂分化成为高达两百多种不同的细胞,而恶性肿瘤细胞,同样的也利用存在的微环境,释出与接收调控生长分裂的讯号,来主导细胞的代谢活动,因此若能利用诱导干细胞发育的想法,确实有机会逆转恶性肿瘤细胞的发育,回复成为正常细胞的可能。
结果研究人员发现当恶性黑色素瘤细胞,会在斑马鱼胚胎干细胞发育的环境中,居然释出了一个称为 Nodal的胚胎因子 (embryonic factor),就过去相关的研究资料显示, Nodal胚胎因子是干细胞之所以具有多能化 (pluripotency)的主要原因,研究人员进一步的阻断 Nodal的分子活动,使得原本分裂失控的恶性黑色素瘤细胞,回复成非常类似于正常皮肤的细胞。
这一个新的突破,结合了原本不相关的两个研究领域,相关科学家认为,也许未来抑制肿瘤的研究,加入了干细胞研究所掌握的知识,就可以轻易的突破了当前治疗的瓶颈。
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