scholarly journals Breast Cancer Tumor Stroma: Cellular Components, Phenotypic Heterogeneity, Intercellular Communication, Prognostic Implications and Therapeutic Opportunities

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 664 ◽  
Author(s):  
Noemi Eiro ◽  
Luis O. Gonzalez ◽  
María Fraile ◽  
Sandra Cid ◽  
Jose Schneider ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Disease ◽  
Tumor Stroma ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Matrix Metalloproteases ◽  
Relevant Role ◽  
Cancer Tumor ◽  
Prognostic Implications ◽  
Cellular Components

Although the mechanisms underlying the genesis and progression of breast cancer are better understood than ever, it is still the most frequent malignant tumor in women and one of the leading causes of cancer death. Therefore, we need to establish new approaches that lead us to better understand the prognosis of this heterogeneous systemic disease and to propose new therapeutic strategies. Cancer is not only a malignant transformation of the epithelial cells merely based on their autonomous or acquired proliferative capacity. Today, data support the concept of cancer as an ecosystem based on a cellular sociology, with diverse components and complex interactions between them. Among the different cell types that make up the stroma, which have a relevant role in the dynamics of tumor/stromal cell interactions, the main ones are cancer associated fibroblasts, endothelial cells, immune cells and mesenchymal stromal cells. Several factors expressed by the stroma of breast carcinomas are associated with the development of metastasis, such as matrix metalloproteases, their tissular inhibitors or some of their regulators like integrins, cytokines or toll-like receptors. Based on the expression of these factors, two types of breast cancer stroma can be proposed with significantly different influence on the prognosis of patients. In addition, there is evidence about the existence of bi-directional signals between cancer cells and tumor stroma cells with prognostic implications, suggesting new therapeutic strategies in breast cancer.

scholarly journals The Effects of Chemotherapeutics on the Ovarian Cancer Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3136
Author(s):  
Mark A. Eckert ◽  
Carlos Orozco ◽  
Jason Xiao ◽  
Melissa Javellana ◽  
Ernst Lengyel
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Cell Types ◽  
Parp Inhibitors ◽  
Chemotherapeutic Agents ◽  
Cancer Types ◽  
Cellular Components ◽  
Target Cancer

High-grade serous ovarian cancer (HGSOC) is characterized by a complex and dynamic tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and adipocytes. Although most approved therapies target cancer cells, a growing body of evidence suggests that chemotherapeutic agents have an important role in regulating the biology of the diverse cells that compose the TME. Understanding how non-transformed cells respond and adapt to established therapeutics is necessary to completely comprehend their action and develop novel therapeutics that interrupt undesired tumor–stroma interactions. Here, we review the effects of chemotherapeutic agents on normal cellular components of the host-derived TME focusing on CAFs. We concentrate on therapies used in the treatment of HGSOC and synthesize findings from studies focusing on other cancer types and benign tissues. Agents such as platinum derivatives, taxanes, and PARP inhibitors broadly affect the TME and promote or inhibit the pro-tumorigenic roles of CAFs by modifying the bidirectional cross-talk between tumor and stromal cells in the tumor organ. While most chemotherapy research focuses on cancer cells, these studies emphasize the need to consider all cell types within the tumor organ when evaluating chemotherapeutics.

scholarly journals Joint Tumor Bud–MMP/TIMP Count at the Invasive Front Improves the Prognostic Evaluation of Invasive Breast Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 196
Author(s):  
Luis O. González ◽  
Noemi Eiro ◽  
María Fraile ◽  
Rosario Sánchez ◽  
Alejandro Andicoechea ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Prognostic Significance ◽  
Tumor Stroma ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Matrix Metalloproteases ◽  
Tumor Budding ◽  
High Grade ◽  
Invasive Front ◽  
Prognostic Evaluation

Background: Tumor budding is a histological phenomenon consisting of the formation of small clusters of one to five undifferentiated malignant cells detached from the main tumor mass which are observed in the tumor stroma. In the present study, we investigated the prognostic significance of tumor budding in breast cancer and its relationship with the expressions of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs). Methods: The number of buds was counted in whole-tissue sections from 153 patients with invasive ductal carcinomas who underwent a long follow-up period. In addition, an immunohistochemical study of MMP-9, -11, and -14 TIMP-1 and -2 expression by cell types at the invasive tumor front was carried out. Results: There was a wide variability in the number of buds among tumors, ranging from 0 to 28 (median = 5). Tumor budding count ≥ 4 was the optimal cut-off to predict both relapse-free and overall survival. High-grade tumor budding was associated with MMP/TIMP expression by cancer-associated fibroblasts. In addition, we found that the combination of tumor budding grade with MMP/TIMP expression by stromal cells, and especially with MMP-11 expression by mononuclear inflammatory cells, significantly improved the prognostic evaluation. Conclusion: High-grade tumor budding is associated with a more aggressive tumor phenotype, which, combined with MMP/TIMP expression by stromal cells at the invasive front of the tumor, identifies patients with poor prognosis.

The IGF system and breast cancer.

2001 ◽  
pp. 197-209 ◽  
Author(s):  
D Sachdev ◽  
D Yee
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Regulatory Pathway ◽  
Breast Epithelial Cells ◽  
Igf System ◽  
System Components ◽  
Igf I

The IGF system components have been implicated in breast cancer progression. IGF-I and IGF-II are mitogenic and anti-apoptotic peptides that influence the proliferation of various cell types including normal and transformed breast epithelial cells. The IGF system is a key growth regulatory pathway in breast cancer. As various components of the IGF system have been directly or indirectly implicated in breast cancer, it is essential to gain a better understanding of these in order to develop more specific therapeutic strategies for treating breast cancer.

scholarly journals Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq

2018 ◽  
Author(s):  
Jianhua Yin ◽  
Zhisheng Li ◽  
Chen Yan ◽  
Enhao Fang ◽  
Ting Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Cell Types ◽  
Rna Seq ◽  
Breast Cancer Patients ◽  
Numerous Cell ◽  
Cancer Tumor

AbstractThe tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. We profiled the breast cancer tumor microenvironment by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. This study explores the diversity of the cell types in the tumor microenvironment and provides information on the mechanisms of escape from clearance by immune cells in breast cancer.One Sentence SummaryLandscape of tumor cells and immune cells in breast cancer by single cell RNA-seq

scholarly journals Immunohistochemical Expression of CD68 in Triple Negative Invasive Ductal Carcinoma of the Breast and its Correlation with Clinicopathological Parameters

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 6-6
Author(s):  
AA Khalaf ◽  
GA Fadaly ◽  
AI El-Sarha ◽  
AF El-Karmouty
Keyword(s):  
Breast Cancer ◽  
Invasive Ductal Carcinoma ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Tumor Grade ◽  
Tumor Stroma ◽  
Clinicopathological Parameters ◽  
Immunohistochemical Expression ◽  
Cancer Tumor

Introduction: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer associated with a poor prognosis. No targeted treatment is available for this subtype. Tumor microenvironment (TME) has been increasingly considered a diagnostic and a prognostic biomarker and a therapeutic target for breast cancer. Tumor associated macrophages (TAM) are a pivotal member of TME and have been proposed as potential targets of therapy. Material and Methods: The immunohistochemical expression of CD68+ve TAM was studied in both tumor stroma (TS) and tumor nest (TN) in 50 cases of triple negative invasive ductal carcinoma as well as in 10 control cases of benign breast lesions. Results: The cases were divided into high or low density groups according to the median. The median in CD68+ve TAM in TS was (61.88), while in CD68+ve TAM in TN was (49.88). The expression of CD68+ve TAM in TS was low in 22 cases and high in 28 cases, while its expression in TN was low in 35 cases and high in 15 cases. There was no statistical association between high CD68+ve TAM in TN and different clinicopathological parameters, meanwhile a statistically significant association was found between high CD68 +ve TAM in TS and tumor grade, lymph/vascular invasion and lymph node metastasis. Conclusions: High expression of TAM in TS, but not in TN, is of clinical significance in patients with TNBC and highlights the importance of analyzing the localization rather than merely the presence of TAM as a marker for prognosis and a potential target for future treatment of triple negative breast cancer.

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