Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers.
Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers.
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整联蛋白和上皮间质合作在肌肉侵入性致命癌的肿瘤微环境中。
DOI：
10.3389/fcell.2022.837585
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发表时间：
2022
影响因子：
5.5
通讯作者：
Cress AE
中科院分区：
文献类型：
--
作者：
Harryman WL;Marr KD;Nagle RB;Cress AE
肌肉浸润性致命癌穿过并穿过这种专门的生物物理和生长因子富集的微环境。我们将重点介绍起源于被平滑肌包围的器官的癌症，平滑肌是扩散的屏障，包括前列腺癌、膀胱癌、食管癌、胃癌和结直肠癌。我们认为细胞-细胞和细胞-ECM粘附受体的异质性是侵袭性肿瘤网络的重要驱动因素，其功能后果是进展。肿瘤的表型异质性为肿瘤网络通过张力肌的侵袭和肿瘤网络的存活提供了生物物理优势。我们假设，一个功能性的上皮间质合作（EMC）存在于肿瘤侵袭网络，以促进肿瘤逃离原发器官，入侵和穿越肌肉，并导航到转移部位。特定的上皮细胞在肿瘤和基质（间充质）细胞与肿瘤的相互作用之间的合作，说明使用层粘连蛋白结合粘附分子，特别是整合素的例子和他们的反应，在肿瘤微环境中的生长和炎症因子。在与侵袭性疾病相关的低分化人类肿瘤中，细胞-细胞（E-钙粘蛋白，CDH 1）和细胞-ECM（α6整联蛋白，CD 49 f）表达与生长因子受体之间的合作突出显示。检查癌症相关成纤维细胞在肿瘤微环境中产生和组织各种生长因子的作用。细胞结构蛋白是未来空间轮廓研究的潜在实用标记物。我们还研究了平滑肌微环境的特殊性，以及原发性肿瘤的侵袭如何改变这种环境，并通过上皮细胞和基质细胞之间的合作促进肿瘤逃逸。这种合作状态允许异质性肿瘤簇通过各种生长因子形成，共同选择或逃避免疫系统反应，从低氧适应常氧条件，适应不同的能量来源，并在放射和化疗干预中存活。了解早期肿瘤侵袭性网络中的上皮-间充质合作对于鉴定侵袭性转变的早期生物标志物和鉴定预防上皮-间充质合作表型的新型药物具有潜力。上皮-间充质合作可能揭示新的肿瘤亚型，以帮助选择适当的治疗策略。
Muscle-invasive lethal carcinomas traverse into and through this specialized biophysical and growth factor enriched microenvironment. We will highlight cancers that originate in organs surrounded by smooth muscle, which presents a barrier to dissemination, including prostate, bladder, esophageal, gastric, and colorectal cancers. We propose that the heterogeneity of cell-cell and cell-ECM adhesion receptors is an important driver of aggressive tumor networks with functional consequences for progression. Phenotype heterogeneity of the tumor provides a biophysical advantage for tumor network invasion through the tensile muscle and survival of the tumor network. We hypothesize that a functional epithelial-mesenchymal cooperation (EMC)exists within the tumor invasive network to facilitate tumor escape from the primary organ, invasion and traversing of muscle, and navigation to metastatic sites. Cooperation between specific epithelial cells within the tumor and stromal (mesenchymal) cells interacting with the tumor is illustrated using the examples of laminin-binding adhesion molecules—especially integrins—and their response to growth and inflammatory factors in the tumor microenvironment. The cooperation between cell-cell (E-cadherin, CDH1) and cell-ECM (α6 integrin, CD49f) expression and growth factor receptors is highlighted within poorly differentiated human tumors associated with aggressive disease. Cancer-associated fibroblasts are examined for their role in the tumor microenvironment in generating and organizing various growth factors. Cellular structural proteins are potential utility markers for future spatial profiling studies. We also examine the special characteristics of the smooth muscle microenvironment and how invasion by a primary tumor can alter this environment and contribute to tumor escape via cooperation between epithelial and stromal cells. This cooperative state allows the heterogenous tumor clusters to be shaped by various growth factors, co-opt or evade immune system response, adapt from hypoxic to normoxic conditions, adjust to varying energy sources, and survive radiation and chemotherapeutic interventions. Understanding the epithelial-mesenchymal cooperation in early tumor invasive networks holds potential for both identifying early biomarkers of the aggressive transition and identification of novel agents to prevent the epithelial-mesenchymal cooperation phenotype. Epithelial-mesenchymal cooperation is likely to unveil new tumor subtypes to aid in selection of appropriate therapeutic strategies.
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影响因子：
19
作者：
Bakir B;Chiarella AM;Pitarresi JR;Rustgi AK
通讯作者：
Rustgi AK
EMT亚型影响上皮可塑性和细胞迁移模式。
影响因子：
11.8
作者：
Aiello NM;Maddipati R;Norgard RJ;Balli D;Li J;Yuan S;Yamazoe T;Black T;Sahmoud A;Furth EE;Bar-Sagi D;Stanger BZ
通讯作者：
Stanger BZ
影响因子：
4.8
作者：
Carracedo, Sergio;Lu, Ning;Gullberg, Donald
通讯作者：
Gullberg, Donald
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT
DOI：
10.4103/jomfp.jomfp_146_15
发表时间：
2017-09-01
期刊：
Journal of oral and maxillofacial pathology : JOMFP
影响因子：
--
作者：
Bagalad, Bhavana S;Mohan Kumar, K P;Puneeth, H K
通讯作者：
Puneeth, H K