Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines.
Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines.
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DOI：
10.1186/bcr2755
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Kuperwasser C
中科院分区：
文献类型：
--
作者：
Keller PJ;Lin AF;Arendt LM;Klebba I;Jones AD;Rudnick JA;DiMeo TA;Gilmore H;Jefferson DM;Graham RA;Naber SP;Schnitt S;Kuperwasser C
正常和肿瘤性乳腺组织由不同程度成熟和分化的异质上皮细胞组成。虽然培养的细胞系既来自正常组织，也来自恶性组织，但目前尚不清楚它们在多大程度上保留了与乳腺组织相似的分化和异质性。我们以12例乳房缩小术组织、15例原发乳腺癌组织和20株人乳腺上皮细胞株(16株癌细胞，4株正常乳腺细胞株)为研究对象，采用流式细胞术检测CD44、CD24、上皮细胞黏附分子(EpCAM)和CD49f的表达，并进行免疫组织化学和体内移植瘤研究，以深入分析乳腺上皮细胞系的分子和细胞特性。人类乳腺组织包含四种不同的上皮分化状态(两种腔表型和两种基本表型)，它们基于CD24、EpCAM和CD49f的表达而不同。原发人类乳腺癌组织也包含这四种细胞状态，但与正常组织相比比例发生了变化。相比之下，培养的癌细胞系富含稀有的基底层和间质上皮表型，这些表型通常在人体组织中少量存在。同样，培养的正常人类乳腺上皮细胞系富含稀有的基底层和间质表型，这些表型代表了缩乳术组织中的一小部分细胞。此外，尽管正常的人乳腺上皮细胞株表现出双能祖细胞的特征，但它们在标准培养条件下无法分化为成熟的管腔上皮细胞。作为一个群体，乳腺癌细胞系代表了人类乳腺肿瘤的异质性，但就个别而言，它们表现出更多的谱系限制，不能真正代表单个乳腺肿瘤的肿瘤内异质性。此外，正常的人类乳腺上皮细胞株不能保留人类乳腺组织中的大部分细胞多样性，并为分化状态而丰富，这在乳腺组织中是少数，尽管它们确实表现出双能基本祖细胞的特征。这些发现表明，代表多种细胞类型的细胞系集合可以用来模拟组织的细胞异质性。
Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral heterogeneity of individual breast tumors. Additionally, normal human mammary epithelial cell lines fail to retain much of the cellular diversity found in human breast tissues and are enriched for differentiation states that are a minority in breast tissues, although they do exhibit features of bi-potent basal progenitor cells. These findings suggest that collections of cell lines representing multiple cell types can be used to model the cellular heterogeneity of tissues.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
7.4
作者：
Sheridan, Carol;Kishimoto, Hiromitsu;Fuchs, Robyn K.;Mehrotra, Sanjana;Bhat-Nakshatri, Poornima;Turner, Charles H.;Goulet, Robert, Jr.;Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
DOI：
10.1158/1078-0432.ccr-09-1532
发表时间：
2010-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Park SY;Lee HE;Li H;Shipitsin M;Gelman R;Polyak K
通讯作者：
Polyak K
影响因子：
50.3
作者：
Neve, Richard M.;Chin, Koei;Gray, Joe W.
通讯作者：
Gray, Joe W.