HETEROGENEITY AND MALIGNANT PROGRESSION OF HUMAN BREAST

人类乳腺的异质性和恶变的本质 癌症将通过研究分离出的不同亚群进行评估 短期培养前后的乳腺癌。亚种群 将根据侵袭性、倍性水平、 分化标志物的表达，或细胞间的程度 粘附性。这些从癌症中分离出来的亚群将是 培养的、进一步鉴定的细胞，并与从 恶性进展的极端情况(即正常组织和转移组织 渗出)。侵袭力将使用剥离羊膜试验进行测量； 倍性水平将通过流式细胞术、显微分光光度法、 和核子学。为了测量分化，我们将利用单克隆 乳脂小球抗原的抗体，一种肌上皮抗原， α-乳清蛋白多价抗体与脂质组织化学染色 颗粒。要检查的其他属性，以包括各种 细胞外基质和基因扩增能力。一 我们预计的有趣结果是，我们将拥有 原发癌中的不同亚群，并与 乳腺非恶性上皮细胞特性在乳腺癌中的表达 与恶性有关的文化。通过这种方式，我们将尝试 确定这些表型对乳腺癌的意义，并 确定细胞获取相关属性的顺序(S) 带着恶毒。例如，如果肿瘤通过首先获得 属性“a”，然后是“b”，最后是“c”，则预期 肿瘤获得了属性“a”，而只有一些细胞具有“a”和 “b”或更少的人会表达所有这三个属性。我们建议确定 这一序列适用于许多不同组织学类型的乳腺癌 类型，以了解乳房中表现出的异质性程度 癌症。

The nature of heterogeneity and malignant progression of human breast cancers will be evaluated by studying various subpopulations isolated from mammary carcinomas before and after short term culture. Subpopulations will be selected initially on the basis of invasiveness, ploidy level, expression of differentiation markers, or degree of intercellular adhesiveness. These isolated subpopulations from the carcinomas will be cultured, further characterized, and compared to cells cultured from the extremes of malignant progression, (i.e. normal tissues and metastatic effusions). Invasiveness will be measured using a denuded amnion assay; ploidy levels will be determined by flow cytometry, microspectrophotometry, and karyology. For measuring differentiation, we will utilize monoclonal antibodies to milk fat globule antigen, a myoepithelial antigen, a polyvalent antibody to alpha-lactalbumin and histochemical stain for lipid granules. Other properties to be examined to include behavior on various extracellular matrices, and capacity for gene amplification. One interesting outcome that we anticipate is that we will have characterized various subpopulations within the primary carcinoma and compared them with nonmalignant mammary epithelial cells for expression of properties in culture associated with malignancy. In this way, we will attempt to determine the significance of these phenotypes for breast cancer and also to determine the sequence(s) by which cells acquire properties associated with malignancy. For example, if a tumor progresses by first acquiring property "a", then "b", and finally "c", one would expect most cells in the tumor to have gained property "a" while only some cells would have "a" and "b" and fewer would express all three properties. We propose to determine this sequence for a number of breast carcinomas of different histologic types in order to understand the extent of heterogeneity manifest in breast cancer.