Role of stem cells in human uterine leiomyoma growth.
Role of stem cells in human uterine leiomyoma growth.
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DOI：
10.1371/journal.pone.0036935
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bulun SE
中科院分区：
文献类型：
--
作者：
Ono M;Qiang W;Serna VA;Yin P;Coon JS 5th;Navarro A;Monsivais D;Kakinuma T;Dyson M;Druschitz S;Unno K;Kurita T;Bulun SE
子宫平滑肌瘤是育龄妇女最常见的良性肿瘤。每个平滑肌瘤被认为是良性单克隆肿瘤，由单个转化的子宫肌瘤平滑肌细胞产生；然而，目前尚不清楚是哪种平滑肌瘤细胞类型导致了肿瘤的生长。因此，我们验证了这样一种假设，即一种独特的干细胞/储存库细胞富集群体，被称为平滑肌瘤衍生侧群体（LMSP），负责细胞增殖和肿瘤生长。LMSP约占所有平滑肌瘤的1%，占所有子宫肌源性细胞的2%。所有的LMSP和平滑肌瘤来源的主要群体（LMMP），但从邻近的肌层分离的侧面或主要群体细胞都没有携带中介复合体亚基12突变，这是肿瘤转化的遗传标记。雌激素受体-α、孕激素受体和平滑肌细胞标志物的信使RNA水平在LMSP中几乎检测不到，且与LMMP相比显著降低。在有或没有雌二醇和黄体酮的单层培养中，LMSP不能单独附着或存活，而LMMP在这些条件下很容易生长。在单层培养中，LMSP与未分选的子宫肌瘤细胞直接混合，可以附着并存活。通过诉诸和重组，LMSP充分发挥了扩散潜力。有趣的是，由LMSP和未分选的肌层平滑肌细胞组成的异种移植物生长成相对较大的肿瘤（3.67±1.07 mm3），而由LMMP和未分选的肌层平滑肌细胞组成的异种移植物产生的肿瘤较小（0.54±0.20 mm3, p<0.05, n = 10对患者样本）。LMSP异种移植物的增殖活性显著高于LMMP异种移植物（p<0.05）。我们的数据表明，具有干细胞/库细胞特性的LMSP对于异种平滑肌瘤的体内生长是必需的。LMSP中雌激素和孕激素受体水平较低，表明类固醇激素通过成熟邻近细胞间接对干细胞产生旁分泌作用。
Uterine leiomyoma is the most common benign tumor in reproductive-age women. Each leiomyoma is thought to be a benign monoclonal tumor arising from a single transformed myometrial smooth muscle cell; however, it is not known what leiomyoma cell type is responsible for tumor growth. Thus, we tested the hypothesis that a distinct stem/reservoir cell-enriched population, designated as the leiomyoma-derived side population (LMSP), is responsible for cell proliferation and tumor growth. LMSP comprised approximately 1% of all leiomyoma and 2% of all myometrium-derived cells. All LMSP and leiomyoma-derived main population (LMMP) but none of the side or main population cells isolated from adjacent myometrium carried a mediator complex subunit 12 mutation, a genetic marker of neoplastic transformation. Messenger RNA levels for estrogen receptor-α, progesterone receptor and smooth muscle cell markers were barely detectable and significantly lower in the LMSP compared with the LMMP. LMSP alone did not attach or survive in monolayer culture in the presence or absence of estradiol and progestin, whereas LMMP readily grew under these conditions. LMSP did attach and survive when directly mixed with unsorted myometrial cells in monolayer culture. After resorting and reculturing, LMSP gained full potential of proliferation. Intriguingly, xenografts comprised of LMSP and unsorted myometrial smooth muscle cells grew into relatively large tumors (3.67±1.07 mm3), whereas xenografts comprised of LMMP and unsorted myometrial smooth muscle cells produced smaller tumors (0.54±0.20 mm3, p<0.05, n = 10 paired patient samples). LMSP xenografts displayed significantly higher proliferative activity compared with LMMP xenografts (p<0.05). Our data suggest that LMSP, which have stem/reservoir cell characteristics, are necessary for in vivo growth of leiomyoma xenograft tumors. Lower estrogen and progesterone receptor levels in LMSP suggests an indirect paracrine effect of steroid hormones on stem cells via the mature neighboring cells.
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影响因子：
3.7
作者：
Hodge, Jennelle C.;Park, Peter J.;Dreyfuss, Jonathan M.;Assil-Kishawi, Iman;Somasundaram, Priya;Semere, Luwam G.;Quade, Bradley J.;Lynch, Allison M.;Stewart, Elizabeth A.;Morton, Cynthia C.
通讯作者：
Morton, Cynthia C.
影响因子：
20.3
作者：
Quesenberry, PJ;Colvin, GA;Lambert, JF
通讯作者：
Lambert, JF
影响因子：
64.8
作者：
Asselin-Labat, Marie-Liesse;Vaillant, Francois;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
2.9
作者：
Kurita, T;Medina, R;Gold, LI
通讯作者：
Gold, LI
DOI：
10.1177/1933719109348924
发表时间：
2010-02
期刊：
Reproductive sciences (Thousand Oaks, Calif.)
影响因子：
--
作者：
Chang HL;Senaratne TN;Zhang L;Szotek PP;Stewart E;Dombkowski D;Preffer F;Donahoe PK;Teixeira J
通讯作者：
Teixeira J