为什么肿瘤总转移到肺？

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                    <section data-role="paragraph" data-color="rgb(182, 228, 253)" data-custom="rgb(182, 228, 253)"><section><section><section><section powered-by="gulangu"><section><section><section><section powered-by="gulangu"><section><section><section><section powered-by="gulangu"><section><section><section><section powered-by="gulangu"><section><section><section><section><p><p><img src="image/20201014/86b79d371e9862b01189f0252a03b2cd_1.png" /></p></p></section><section><section><span><strong></strong></span></section><p><span>医疗器械媒体报道先锋</span></p><p><span>分享专业医疗器械知识</span></p></section><section><section><section><span>关注</span></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section></section><p><p><img src="image/20201014/f276872b64f98c4bbf5aaecd10b4777c_2.jpg" /></p></p><p><br  /></p><section powered-by="gulangu"><section><section data-role="outer" label="Powered by gulangu"><section data-tools="gulangu" data-id="94721" data-color="#757576"><section data-width="97%"><section><section></section><section data-autoskip="1"><p><span><strong><span>在癌症转移中，肺部是最受青睐的器官之一</span></strong><span>。乳腺癌、结肠癌、肾癌、胃癌等多种癌症类型，常常把肺部作为转移的目标。</span></span></p><p><br  /></p><p><span>除此之外，肺癌也是世界范围内最高发的癌症，<strong>是癌症相关死亡的最主要原因</strong>。</span></p><p><br  /></p><p><span>可以说，包括原发性肺癌和继发性肺癌（其他癌症肺转移）在内的肺部相关癌症，已经成为一个重要的全球健康问题。</span></p><p><br  /></p><p><span>那么，你想不想知道，为什么在癌症转移中肺转移最常发生？又是何种机制促进了肺部相关癌症的发生与发展？</span></p><p><br  /></p><p><span>让我们接着看下去。</span></p><p><br  /></p></section></section><section data-bgless="spin" data-bglessp="20"></section></section></section><section data-role="paragraph"><p><br  /></p></section></section></section></section><section powered-by="gulangu"><section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><section><section powered-by="gulangu"><section><section><p><img src="image/20201014/e9fcd6269d5b3b623903dc012920820d_3.png" /></p></section></section></section><section powered-by="gulangu"><section><section powered-by="gulangu"><p><span><strong>半分钟读全文</strong><strong></strong></span></p></section><section powered-by="gulangu"><section></section><section><section powered-by="gulangu"><ul><li><p><span>肿瘤微环境通过促进炎症，血管生成和免疫调节来实现肺部相关癌症的发生与发展。</span></p></li><li><p><span>香烟烟雾引起的炎症与小鼠和人类原发性乳腺癌的肺转移增加有关。</span><br  /></p></li><li><p><span>散播肿瘤细胞的转移性生长需要血管生成的支持。</span></p></li><li><p><span>引起广泛关注的免疫疗法，其目标旨在改善免疫细胞的功能或抑制免疫抑制的活性。</span><br  /></p></li><li><p><span>肿瘤重编程的肺部微环境是非常适宜肿瘤细胞生长的沃土，针对于肿瘤重编程的肺部微环境的药物开发，开创了癌症医学的新时代。</span><span></span></p></li></ul></section></section></section></section></section></section></section><section powered-by="gulangu"><p><br  /></p></section></section></section><section powered-by="gulangu"><section><section><p><span><strong>什么是肺部肿瘤微环境？</strong><strong></strong></span></p></section></section></section><section powered-by="gulangu"><section><p><span>在过去的十年中，人们逐渐认识到肺部肿瘤微环境在肺部相关癌症的发生与发展中起到核心作用。</span><br  /></p></section></section><section powered-by="gulangu"><section><p><span><span>肿瘤微环境通常是指肿瘤“生态环境”中的所有非恶性宿主细胞和非细胞组分，</span><strong>包括但不限于癌症相关成纤维细胞（CAF）、细胞外基质（ECM）、内皮细胞和浸润性免疫细胞</strong><span>。</span></span><br  /></p><p><br  /></p><p><span>早在一个世纪之前，英国医生佩吉特提出“<strong>种子和土壤”</strong>的假说，认为肿瘤的转移会受到微环境相互作用的影响，<span><strong>肿瘤必须具有适应远处微环境的能力，才能够实现发生与发展</strong></span>。</span></p><p><br  /></p></section></section><section powered-by="gulangu"><section><p><img src="image/20201014/9c589f5da13ac5afcb2f02dfeb243ab6_4.jpg" /></p></section></section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><section><section></section><section></section><section><section><section powered-by="gulangu"><section><p><span><strong>癌症相关成纤维细胞</strong><strong></strong></span></p><p><br  /></p><p><span>人类非小细胞肺癌通常表现出结缔组织形成，这就是由于癌症相关成纤维细胞的存在。</span><span>其介导着癌细胞的增殖、血管生成、侵袭及转移。</span><span>此外，癌症相关成纤维细胞还可以调节肿瘤微环境中的免疫应答。</span></p></section></section></section></section></section></section><section powered-by="gulangu"><section><section></section><section></section><section><section><section powered-by="gulangu"><section><p><span><strong>细胞外基质</strong><strong></strong></span></p><p><br  /></p><p><span>由胶原蛋白、蛋白聚糖和糖胺聚糖组成，是肿瘤微环境的主要成分。</span><span>其介导着癌细胞和基质细胞之间的相互作用，从而导致癌症形成。</span></p></section></section></section></section></section></section><section powered-by="gulangu"><section><section></section><section></section><section><section><section powered-by="gulangu"><section><p><span><strong>内皮细胞</strong><strong></strong></span></p><p><br  /></p><p><span>血管生成，是指先前存在的脉管系统中形成了新的血管，是癌症的关键标志。</span><span>血管生成相关因子可以促进内皮细胞的迁移和增殖，导致支持肿瘤进展、侵袭和转移的新毛细血管形成。</span></p></section></section></section></section></section></section><section powered-by="gulangu"><section><section></section><section></section><section><section><section powered-by="gulangu"><section><p><span><strong>免疫肿瘤微环境</strong><strong></strong></span></p><p><br  /></p><p><span>肺部肿瘤微环境中的先天性和适应性免疫细胞具有促进肿瘤和抑制肿瘤的活性，包括骨髓细胞群、淋巴细胞群等。</span></p></section></section></section></section></section></section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><p><span>当然，其他癌症转移病灶之所以青睐肺部，除了肺部肿瘤微环境非常具有“亲和力”外，还有一个重要原因，就是<strong>肺循环占据了全身循环血量的大半，并拥有大面积的毛细血管利于循环肿瘤细胞滞留</strong>。</span></p><p><br  /></p><p><span>也就是说，散播的肿瘤细胞常常会把肺部作为转移这趟“旅行”的目的地。</span></p></section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><section><section><p><span><strong>肿瘤微环境如何促进肺部相关癌症的发生与发展？</strong><strong></strong></span></p></section></section></section><section powered-by="gulangu"><section><p><span>除了原发性肺部肿瘤，包括乳腺癌、结肠癌、以及皮肤癌在内的恶性肿瘤也可以通过分泌多种因子，<span><strong>系统性地重编程肺部肿瘤微环境以产生适宜转移的生态环境（转移前生态位）</strong></span>。</span></p><p><br  /></p><p><span>小鼠模型的研究表明，这些转移前生态位主要基于宿主免疫系统、炎症细胞、器官特异性化学引诱物和生长因子等<strong>为散播肿瘤细胞提供支持外渗、定植和转移生长的适宜微环境</strong>。</span></p><p><br  /></p></section></section><section powered-by="gulangu"><section><p><img src="image/20201014/2b42e0e5ddf12f02b71731069c04ca3e_5.jpg" /></p></section></section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><section><section powered-by="gulangu"><section><p><span><strong>促进炎症</strong><strong></strong></span></p></section></section></section></section><section powered-by="gulangu"><section><p><span>暴露于香烟烟雾而引起的肺部炎症可能导致转移增加。</span><span>例如，<strong>香烟烟雾引起的炎症与小鼠和人类原发性乳腺癌的肺转移增加有关</strong>。</span></p><p><br  /></p><p><span>有流行病学证据和临床试验结果表明，长期使用阿司匹林与癌症死亡率降低相关。</span></p><p><br  /></p></section></section><section powered-by="gulangu"><section><section powered-by="gulangu"><section><p><span><strong>血管生成</strong><strong></strong></span></p></section></section></section></section><section powered-by="gulangu"><p><span>散播肿瘤细胞的转移性生长受到血管生成的支持，主要是通过浸润骨髓来源的内皮祖细胞或VEGF受体的磷酸化来介导。</span></p><p><br  /></p><p><span><strong><span>VEGF途径是肿瘤血管生成的关键介质</span></strong><span>，目前已经开发出靶向该途径的多种血管生成抑制剂。贝伐珠单抗就是一种血管生成抑制剂，其于2006年获FDA批准，与卡铂和紫杉醇联合用于晚期非鳞状非小细胞肺癌的一线治疗。&nbsp;</span></span></p><p><br  /></p></section><section powered-by="gulangu"><section><section powered-by="gulangu"><section><p><span><strong>免疫调节</strong><strong></strong></span></p></section></section></section></section><section powered-by="gulangu"><p><span>以NK细胞为例，NK细胞在肿瘤免疫监视和转移控制中发挥作用，肿瘤细胞衍生的CCL2细胞因子通过抑制NK细胞的细胞毒性和成熟程度，产生了免疫抑制的转移前生态位。</span></p><p><br  /></p><p><span>而目前引起广泛关注的免疫疗法，其目标旨在<strong>改善免疫细胞的功能或抑制免疫抑制的活性</strong>。</span></p><p><br  /></p><p><span>以Opdivo和Keytruda为首的免疫检查点抑制剂，恢复了T细胞介导的抗肿瘤免疫，改变了包括肺癌在内的多种实体肿瘤的实践指南。&nbsp; &nbsp;</span></p><p><br  /></p></section><section powered-by="gulangu"><p><br  /></p></section><section powered-by="gulangu"><section><section><p><span><strong>写在最后</strong><strong></strong></span></p></section></section></section><section powered-by="gulangu"><section><p><span>为什么在癌症转移中，肺部常常最容易“受伤”？</span></p><p><br  /></p><p><span><span>也许可以这样理解，</span><strong>肿瘤重编程的肺部微环境成为了非常适宜肿瘤细胞生长的沃土</strong><span>，因此众多肿瘤细胞纷纷前来，“生根发芽”。</span></span><br  /></p><p><br  /></p><p><span>肺部的复杂微环境在原发性肺癌和继发性肺癌的发展中起到至关重要的作用。<strong>对于肿瘤重编程的肺部微环境的理解和药物开发，开创了癌症医学的新时代</strong>。</span></p></section></section><p><br  /></p><p><span>内容已获授权，如需转载请联系美中嘉和肿瘤防治</span></p><p><br  /></p><p><span><strong><span><a data-miniprogram-appid="wxdc7efe409d688f37" data-miniprogram-path="pages/authorizationLogin/authorizationLogin" data-miniprogram-nickname="" href="" data-miniprogram-type="image" data-miniprogram-servicetype="" target="_blank" href=""><p><img src="image/20201014/7235eecc5e3d188f5fff3d4fc9e8c241_6.png" /></p></a></span></strong></span></p><p><br  /></p><section data-id="1658"><section><section><section data-id="1658"><section><section><section data-id="1658"><section><section><section data-id="1658"><section><section><p><span><strong>相关阅读</strong></span></p></section><p><p><img src="image/20201014/ec237188ae1e9c03eb4d9814f31b18ab_7.gif" /></p></p><p><br  /></p><p><span>【图说】各种医学美图，笑cry</span></p><p><br  /></p><p><span>不讨喜的蛇是怎么“混进”医学logo的？</span><br  /></p><p><br  /></p></section></section></section></section></section></section></section></section></section></section></section><p><br  /></p><p><br  /></p><p><p><img src="image/20201014/cd6e6da350853c459044672a7cf353fb_8.jpg" /></p></p>