当缺氧时，肿瘤似乎应当缩减少，然而，大量研究已证实肿瘤缺氧的情况下，肿瘤部分区域含有极低浓度的氧气，反而会增加肿瘤的侵袭性行为和显示出更差的预后。这似乎表明肿瘤不会屈服于缺氧，相反肿瘤的过量增加血液供应，因而经常会导致缺氧，从而给肿瘤发送生长和转移的信号以便寻找新的氧气源。比如，缺氧性膀胱癌可能转移到肺部，而这经常是致命性的。

　　在一项刊登在《Cancer Research》期刊上的最新研究中，美国科罗拉多大学癌症中心研究人员在详细地描述了这些缺氧条件导致侵袭性癌症产生的机制。

　　论文通信作者Dan Theodorescu博士说，“我们已经知道蛋白HIF-1a在缺氧性肿瘤中过量表达。我们也已经知道癌干细胞标记物CD24在很多肿瘤中过量表达。这项研究证实这两者之间存在关联：缺氧性肿瘤中的HIF-1a导致CD24过量表达。也正是CD24让肿瘤表现出侵袭性的生长和转移特征。”

　　过量增加血液供应会导致肿瘤缺氧，而肿瘤缺氧导致HIF-1a过量表达。HIF-1a过量表达会促进CD24产生，从而导致肿瘤生长和转移。除了让肿瘤变得更具侵袭性之外，研究人员还证实CD24让肿瘤对化疗产生耐药性，从而当化疗结束时，允许一小部分细胞---即前面提到的癌干细胞---再生肿瘤，而这又会导致肿瘤复发和恶化。

　　Theodorescu说，“如今想象一下我们靶向CD24。不论是通过移除细胞表达CD24的能力，还是杀死以这种蛋白为标记物的细胞，我们可能都能够破坏这些最为危险性的细胞群体。”

　　Theodorescu和同事们通过调整癌细胞样品和模式动物中的HIF-1a和CD24水平而证实了这一点：让HIF-1a保持较低水平，但人为让CD24保持较高水平，癌细胞保持再生和转移的能力；相反，让CD24保持较低水平，但人为让HIF-1a保持较高水平，癌细胞存活和增殖能力下降。

　　Theodorescu说，“这似乎表明在缺氧性肿瘤中，处于缺氧之中的细胞过量表达CD24，这会促进癌症生长和转移。如今，我们为这些缺氧性肿瘤找到一个合理的靶标，即CD24。”

　　CD24 is an effector of HIF-1 driven primary tumor growth and metastasis

　　Shibu Thomas1, Michael Harding1, Steven C Smith2, Jonathan B Overdevest3, Matthew D. Nitz3, Henry F Frierson Jr4, Scott A Tomlins5, Glen Kristiansen6, and Dan Theodorescu

　　Hypoxia drives malignant progression in part by promoting accumulation of the oncogenic transc**tion factor HIF-1α in tumor cells. Tumor aggressiveness also relates to elevation of the cancer stem cell-associated membrane protein CD24, which has been causally implicated in tumor formation and metastasis in experimental models. Here we link these two elements by showing that hypoxia induces CD24 expression through a functional hypoxia responsive element (HRE) in the CD24 promoter. HIF-1α overexpression induced CD24 mRNA and protein under normoxic conditions, with this effect traced to a recruitment of endogenous HIF-1α to the CD24 promoter. shRNA mediated-attenuation of HIF-1α or CD24 expression reduced cancer cell survival in vitro and in vivo at the levels of primary and metastatic tumor growth. CD24 overexpression in HIF-1α-depleted cancer cells rescued this decrease while HIF-1α overexpression in CD24-depleted cells did not. Analysis of clinical tumor specimens revealed a correlation between HIF-1α and CD24 levels and an association of their co-expression to decreased patient survival. Our results establish a mechanistic linkage between two critically important molecules in cancer, identifying CD24 as a critical HIF-1α transc**tional target and biological effector, strengthening the rationale to target CD24 for cancer therapy.