Milky Spots Promote Ovarian Cancer Metastatic Colonization of Peritoneal Adipose in Experimental Models
Milky Spots Promote Ovarian Cancer Metastatic Colonization of Peritoneal Adipose in Experimental Models
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DOI：
10.1016/j.ajpath.2013.04.023
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发表时间：
2013-08-01
影响因子：
6
通讯作者：
Rinker-Schaeffert, Carrie
中科院分区：
文献类型：
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作者：
Clark, Robert;Krishnan, Venkatesh;Rinker-Schaeffert, Carrie
控制卵巢癌转移形成的目的引起了人们对确定与癌细胞殖民化的组织微环境的浓厚兴趣。精神脂肪是卵巢癌模型和临床疾病中巨大转移的位置。该组织的乳状斑点是不寻常的，其乳状斑点由免疫细胞，基质细胞和肾小球样毛细管床周围的结构元素组成。本研究表明，乳白色斑点和脂肪细胞在精神转移定殖中起着独特而互补的作用。体内测定表明，ID8，CAOV3，HEYA8和SKOV3IP.1癌细胞优先地养殖并在含有乳白色斑点的膜和脾脏脂肪中生长，而不是在腹膜脂肪库中。同样，与含有乳白色斑点缺陷脂肪的培养基相比，由含乳白色的脂肪组织调节的培养基导致细胞迁移高75％。对免疫缺陷小鼠的研究表明，小鼠遗传背景不会改变精神乳白色点的数量和大小，也不会影响卵巢癌的定殖。最后，与脂质作为癌细胞生长的能源的作用一致，体内时间课程的研究表明，转移负担与精神脂肪细胞含量之间存在反比关系。我们的发现支持了一个两步模型，其中乳白色斑点和脂肪在卵巢癌细胞的卵膜定殖中都具有特定的作用。
The goal of controlling ovarian cancer metastasis formation has elicited considerable interest in identifying the tissue microenvironments involved in cancer cell colonization of the omentum. mental adipose is a site of prodigious metastasis in both ovarian cancer models and clinical disease. This tissue is unusual for its milky spots, comprised of immune cells, stromal cells, and structural elements surrounding glomerulus-like capillary beds. The present study shows the novel finding that milky spots and adipocytes play distinct and complementary roles in mental metastatic colonization. In vivo assays showed that ID8, CaOV3, HeyA8, and SKOV3ip.1 cancer cells preferentially lodge and grow within omental and splenoportal fat, which contain milky spots, rather than in peritoneal fat depots. Similarly, medium conditioned by milky spot-containing adipose tissue caused 75% more cell migration than did medium conditioned by milky spot-deficient adipose. Studies with immunodeficient mice showed that the mouse genetic background does not alter mental milky spot number and size, nor does it affect ovarian cancer colonization. Finally, consistent with the role of Lipids as an energy source for cancer cell growth, in vivo time-course studies revealed an inverse relationship between metastatic burden and mental adipocyte content. Our findings support a two-step model in which both milky spots and adipose have specific roles in colonization of the omentum by ovarian cancer cells.