Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets
| Autor: | Yoshiaki Rai, Minoru Miyashita, Hisashi Hirakawa, Mika Watanabe, Yayoi Takahashi, Saki Nakagawa, Hironobu Sasano, Yasuhiro Miki, Shuko Hata, Yasuaki Sagara, Kentaro Tamaki, Noriaki Ohuchi, Yasuyo Ohi, Takashi Suzuki, Takanori Ishida |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
0301 basic medicine CD31 Cancer Research Pathology medicine.medical_specialty Stromal cell Angiogenesis CD34 Antigens CD34 Breast Neoplasms Cell Cycle Proteins Biology Receptor IGF Type 1 Nestin 03 medical and health sciences 0302 clinical medicine Tumor Microenvironment medicine Humans Insulin-Like Growth Factor I skin and connective tissue diseases Microvessel Aged Neoplasm Staging Aged 80 and over Tumor microenvironment Neovascularization Pathologic Middle Aged medicine.disease Immunohistochemistry Actins Tumor Burden body regions Carcinoma Lobular 030104 developmental biology Oncology 030220 oncology & carcinogenesis Invasive lobular carcinoma Angiogenesis Inducing Agents Female Biomarkers |
| Zdroj: | Breast Cancer Research and Treatment. 155:65-75 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC. |
| Databáze: | OpenAIRE |
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