孕酮是一种调节正常乳房组织生长的雌性激素，但也参与了乳癌的形成。它在致癌过程中的确切作用还不十分清楚。将要发表在《细胞生物化学杂志》上的一项研究中，葡萄牙科学家组成的研究小组表示，孕酮能维持血管形成，后者为肿瘤细胞提供营养，是乳癌演进的关键。该研究结果具有重要意义，不仅有助于更深入了解乳癌，而且蕴含着现在和将来治疗乳癌的方法。
虽然目前乳癌趋向于预后相对良好，但乳癌是世界上第二常见的癌症，每年大约有1百万新发病例。其预后相对良好的原因之一是，大多数乳癌是激素依赖的，阻断激素治疗非常有效，有时甚至超过化疗。
70％－80％原发性乳癌的肿瘤细胞都存在雌二醇和/或孕酮受体。这些受体的作用类似于开关；当雌二醇或孕酮和其特异的受体结合时，这个开关就打开，导致乳癌进展。因此，抗激素治疗（尤其是抗雌二醇治疗）阻断了激素的作用，广泛用于治疗乳癌并获得良好效果。
但是，如果雌二醇已经参与肿瘤的生长，孕酮在乳癌中的作用（孕酮阻断疗法的重要性和具体机制）就不很清楚了。葡萄牙波尔图大学的Raquel Soares, Susana Guerreiro 和 Mónica Botelho发现，对孕酮有反应的乳癌细胞当暴露于孕酮下时就会产生血小板来源的生长因子A（PDGF－A）（已知的一种刺激细胞生长和分化的蛋白）。而且PDGF－A不是直接作用于肿瘤细胞，而是释放至细胞周围，对附近细胞产生影响。
肿瘤细胞和周围环境之间的相互作用对癌症进展是非常重要的。事实上，PDGF－A参与促成新生血管的形成（也称为血管发生）。血管发生是癌组织得以生存的决定性过程，因为如果肿瘤周围没有新生血管供给营养，癌细胞就会营养缺乏和死亡。为了测试PDFG－A是否真正参与了乳癌组织周围血管的形成，Soares和他的同事决定分析平滑肌细胞，而平滑肌细胞已被证实参与了该过程，且具有PDFG－A受体。结果发现PDFA－A增加平滑肌细胞的生长和活力，因此证明PDFA－A和孕酮都有支持血管发生的作用。
Soares及其同事的研究证明，孕酮通过帮助肿瘤细胞附近血管的形成和稳定来刺激肿瘤发生发展。这些新生血管不仅对癌细胞的营养供应有重要作用，而且是肿瘤细胞扩散到身体其他部位的重要“出口”。上述结果表明，当前的抗孕酮治疗阻断癌症进展的机制，其靶向作用不仅在于激素依赖的癌细胞，而且还在于新生血管的形成，因此强调了继续进行抗孕酮治疗的重要性。
New Light Over The Role Of The Hormone Progesterone In Breast Cancer
Main Category: IT / Internet / E-mail News
Article Date: 01 Jan 2007 - 4:00 PST
Progesterone is a female sex hormone known to regulate the growth of normal breast tissue while also seeming to be involved in breast cancer. Its exact role in the carcinogenic process, however, is still unclear. But now, in work about to be published in the "Journal of Cellular Biochemistry", a team of Portuguese scientists shows that progesterone seems to sustain the formation of blood vessels, which, by supplying nutrients to the tumour cells, are vital for breast cancer progression. This finding has important implications not only for a better understanding of the disease, but also for present and future therapeutic approaches against it.
Breast cancer is the second most common cancer in the world with approximately 1 million of new cases every year, even if the disease tends to have a relatively favourable prognosis. One of the reasons for this is the fact that a majority of breast cancers are hormone-dependent, and treatments blocking these hormones (and consequently cancer progression) can be extremely effective, sometimes even more than chemotherapy.
In fact, ovarian hormones known to play an important role in the development of normal breast tissue - such as oestrogen and progesterone - also seem to be involved in breast cancer development, with 70 to 80% of primary breast tumours showing oestrogen and/or progesterone receptors in their cells. These receptors act as on-off switch; when the right molecule (in this case oestrogen or progesterone) binds to its specific receptor, the switch is turned on, leading, in the case of breast cancer, to disease progression. In result, anti-hormonal therapy (especially anti-oestrogen therapy), which blocks the hormones’ action, is widely used against the disease with good results.
But if oestrogen has been clearly associated with cancer growth, the role of progesterone in breast cancer (and consequently the importance and the specific mechanism of progesterone-blocking therapy) is much less clear.
But now Raquel Soares, Susana Guerreiro and Mónica Botelho from the University of Porto in Portugal found that breast cancer cells that respond to progesterone, produce, when exposed to the hormone, Platelet-derived growth factor A (PDGF-A) a protein known to stimulate cell growth and division. Furhermore, PDGF-A did not seem to act directly on the tumour cells, but was instead released into the space outside of the cell suggesting an effect on neighbouring cells.
Interaction between tumour cells and their environment is crucial for cancer progression and in fact PDGF-A has been suggested to be involved in the formation of new blood vessels (also called angiogenesis). Angiogenesis is a process crucial for cancer sustainability since without new blood vessels around the tumour site to supply nutrients, cancerous cells will starve and die. To test if PDGF-A could be in fact involved in the formation of blood vessels around breast cancer tumour sites, Soares and colleagues decided to analyse smooth muscle cells, which are known to be involved in this process while also have been described as having receptors for PDGF-A. And in fact, PDGF-A (and so progesterone) was found to increase the growth and viability of smooth muscle cells confirming a role to both these molecules supporting angiogenesis.
What Soares and colleagues’ work strongly suggest is that progesterone stimulates cancer development by helping the formation and stability of blood vessels formed adjacent to the tumour cells. These new blood vessels are, not only crucial to the supply of nutrients to cancer cells, but also important “exits” for these cells to spread throughout the body. These results show how current anti-progesterone therapies block cancer progression by targeting not only progesterone-dependent cancer cells but also the formation of new blood vessels, and emphasise the importance of continue to pursue anti-progesterone therapeutics.
http://www.medicalnewstoday.com/medicalnews.php?newsid=59703
编辑：蓝色幻想
