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Breast Cancer Stroma

Tina Gruosso, Mathieu Gigoux, Venkata Satya Kumar Manem, Nicholas Bertos, Dongmei Zuo, Irina Perlitch, Sadiq Mehdi Ismail Saleh, Hong Zhao, Margarita Souleimanova, Radia Marie Johnson, Anne Monette, Valentina Munoz Ramos, Michael Trevor Hallett, John Stagg, Réjean Lapointe, Atilla Omeroglu, Sarkis Meterissian, Laurence Buisseret, Gert Van den Eynden, Roberto Salgado, Marie-Christine Guiot, Benjamin Haibe-Kains, Morag Park
Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC with implications for current therapies, including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+ CD8+ T cells, a type I interferon signature, elevated expression of multiple immune inhibitory molecules, including IDO, PD-L1, and good outcome...
February 12, 2019: Journal of Clinical Investigation
Marco Franchi, Valentina Masola, Gloria Bellin, Maurizio Onisto, Konstantinos-Athanasios Karamanos, Zoi Piperigkou
: Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM)...
February 7, 2019: Journal of Clinical Medicine
Sasagu Kurozumi, Kenichi Inoue, Hiroshi Matsumoto, Takaaki Fujii, Jun Horiguchi, Tetsunari Oyama, Masafumi Kurosumi, Ken Shirabe
Predictive utility of tumor-infiltrating lymphocytes (TILs) in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy (NAC) with concurrent trastuzumab remains unclear. We examined TILs grades of pretreatment cancer tissue specimens and residual tumors after NAC with trastuzumab and determined the predictive utility of the TILs grade in pathological complete response (pCR) and the prognostic power of TILs in HER2-positive breast cancer. This cohort study included 128 HER2-positive breast cancer who received NAC with trastuzumab...
February 7, 2019: Scientific Reports
Yahya Ashraf, Hanane Mansouri, Valérie Laurent-Matha, Lindsay B Alcaraz, Pascal Roger, Séverine Guiu, Danielle Derocq, Gautier Robin, Henri-Alexandre Michaud, Helène Delpech, Marta Jarlier, Martine Pugnière, Bruno Robert, Anthony Puel, Lucie Martin, Flavie Landomiel, Thomas Bourquard, Oussama Achour, Ingrid Fruitier-Arnaudin, Alexandre Pichard, Emmanuel Deshayes, Andrei Turtoi, Anne Poupon, Joëlle Simony-Lafontaine, Florence Boissière-Michot, Nelly Pirot, Florence Bernex, William Jacot, Stanislas du Manoir, Charles Theillet, Jean-Pierre Pouget, Isabelle Navarro-Teulon, Nathalie Bonnefoy, André Pèlegrin, Thierry Chardès, Pierre Martineau, Emmanuelle Liaudet-Coopman
BACKGROUND: Triple-negative breast cancer (TNBC) treatment is currently restricted to chemotherapy. Hence, tumor-specific molecular targets and/or alternative therapeutic strategies for TNBC are urgently needed. Immunotherapy is emerging as an exciting treatment option for TNBC patients. The aspartic protease cathepsin D (cath-D), a marker of poor prognosis in breast cancer (BC), is overproduced and hypersecreted by human BC cells. This study explores whether cath-D is a tumor cell-associated extracellular biomarker and a potent target for antibody-based therapy in TNBC...
February 4, 2019: Journal for Immunotherapy of Cancer
Ivy X Chen, Vikash P Chauhan, Jessica Posada, Mei R Ng, Michelle W Wu, Pichet Adstamongkonkul, Peigen Huang, Neal Lindeman, Robert Langer, Rakesh K Jain
Metastatic breast cancers (mBCs) are largely resistant to immune checkpoint blockade, but the mechanisms remain unclear. Primary breast cancers are characterized by a dense fibrotic stroma, which is considered immunosuppressive in multiple malignancies, but the stromal composition of breast cancer metastases and its role in immunosuppression are largely unknown. Here we show that liver and lung metastases of human breast cancers tend to be highly fibrotic, and unlike primary breast tumors, they exclude cytotoxic T lymphocytes (CTLs)...
January 30, 2019: Proceedings of the National Academy of Sciences of the United States of America
Eirikur Briem, Saevar Ingthorsson, Gunnhildur Asta Traustadottir, Bylgja Hilmarsdottir, Thorarinn Gudjonsson
The human female breast gland is composed of branching epithelial ducts that extend from the nipple towards the terminal duct lobular units (TDLUs), which are the functional, milk-producing units of the gland and the site of origin of most breast cancers. The epithelium of ducts and TDLUs is composed of an inner layer of polarized luminal epithelial cells and an outer layer of contractile myoepithelial cells, separated from the vascular-rich stroma by a basement membrane. The luminal- and myoepithelial cells share an origin and in recent years, there has been increasing understanding of how these cell types interact and how they contribute to breast cancer...
January 25, 2019: Journal of Mammary Gland Biology and Neoplasia
Nykia D Walker, Michael Elias, Khadidiatou Guiro, Ranvir Bhatia, Steven J Greco, Margarette Bryan, Marina Gergues, Oleta A Sandiford, Nicholas M Ponzio, Samuel J Leibovich, Pranela Rameshwar
Breast cancer (BC) cells (BCCs) can retain cellular quiescence for decades, a phenomenon referred to as dormancy. BCCs show preference for the bone marrow (BM) where they can remain dormant for decades. Targeting BCCs within the BM is a challenge since the dormant BCCs reside within BM stroma, also residence for hematopoietic stem cells (HSCs). Dormant BCCs could behave as cancer stem cells (CSCs). The CSCs and HSCs are similar by function and also, by commonly expressed genes. The method by which dormant BCCs transition into clinically metastatic cells remains unclear...
January 25, 2019: Cell Death & Disease
Vasileios Askoxylakis, Gino B Ferraro, Mark Badeaux, David P Kodack, Isabelle Kirst, Ram C Shankaraiah, Christina S F Wong, Dan G Duda, Dai Fukumura, Rakesh K Jain
The effective treatment of cerebral metastases from HER2-positive breast cancer remains an unmet need. Recent studies indicate that activated astrocytes and brain endothelial cells exert chemoprotective effects on cancer cells through direct physical interaction. Here we report that the endothelin axis mediates protection of HER2 -amplified brain metastatic breast cancers to the anti-HER2 antibody-drug conjugate ado-trastuzumab emtansine (T-DM1). Macitentan, a dual inhibitor of endothelin receptors A and B, improves the efficacy of T-DM1 against breast cancers grown in the brain...
2019: NPJ Breast Cancer
Kwangil Yim, Hong Sik Park, Dong Min Kim, Youn Soo Lee, Ahwon Lee
PURPOSE: Trastuzumab is an effective treatment for human epidermal growth factor receptor 2 (HER2)-amplified breast cancers. We sought to develop a simple protocol for HER2 image analysis of breast cancer specimens. MATERIALS AND METHODS: In a preliminary test, we found that at least 1000 tumor cells need to be examined in the most strongly stained areas. Next, we evaluated the clinical usefulness of this established protocol of image analysis in 555 breast cancer patients...
February 2019: Yonsei Medical Journal
Karla C Williams, Mario A Cepeda, Sumreen Javed, Karlee Searle, Katie M Parkins, Ashley V Makela, Amanda M Hamilton, Sepideh Soukhtehzari, Yohan Kim, Alan B Tuck, John A Ronald, Paula J Foster, Ann F Chambers, Hon S Leong
Invadopodia are cell protrusions that mediate cancer cell extravasation but the microenvironmental cues and signaling factors that induce invadopodia formation during extravasation remain unclear. Using intravital imaging and loss of function experiments, we determined invadopodia contain receptors involved in chemotaxis, namely GABA receptor and EGFR. These chemotaxis capabilities are mediated in part by PAK1 which controls invadopodia responsiveness to ligands such as GABA and EGF via assembly, stability, and turnover of invadopodia in vivo...
January 16, 2019: Oncogene
K Louault, T L Bonneaud, C Séveno, P Gomez-Bougie, F Nguyen, F Gautier, N Bourgeois, D Loussouarn, O Kerdraon, S Barillé-Nion, P Jézéquel, M Campone, M Amiot, P P Juin, F Souazé
Selective inhibition of BCL-2 is expected to enhance therapeutic vulnerability in luminal estrogen receptor-positive breast cancers. We show here that the BCL-2 dependency of luminal tumor cells is nevertheless mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defines MCL-1 as another critical therapeutic target. bCAFs favor MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relies on MCL-1. Studies based on ex vivo cultures of human luminal breast cancer tissues further argue that the contribution of stroma-derived signals to MCL-1 expression shapes BCL-2 dependency...
January 10, 2019: Oncogene
Tamás Deli, Mónika Orosz, Attila Jakab
Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT)...
January 8, 2019: Pathology Oncology Research: POR
Caitlin E Jones, Anisha M Hammer, YouJin Cho, Gina M Sizemore, Edna Cukierman, Lisa D Yee, Samir N Ghadiali, Michael C Ostrowski, Jennifer L Leight
The organization of the extracellular matrix has a profound impact on cancer development and progression. The matrix becomes aligned throughout tumor progression, providing "highways" for tumor cell invasion. Aligned matrix is associated with breast density and is a negative prognostic factor in several cancers; however, the underlying mechanisms regulating this reorganization remain poorly understood. Deletion of the tumor suppressor Pten in the stroma was previously shown to promote extracellular matrix expansion and tumor progression...
December 11, 2018: Neoplasia: An International Journal for Oncology Research
Ramesh Butti, Vinoth Prasanna Gunasekaran, Totakura V S Kumar, Pinaki Banerjee, Gopal C Kundu
Breast cancer remains to be a dreadful disease even with several advancements in radiation and chemotherapies, owing to the drug resistance and tumor relapse caused by breast cancer stem cells. Cancer stem cells are a minute population of cells of solid tumors which show self-renewal and differentiation properties as well as tumorigenic potential. Several signaling pathways including Notch, Hippo, Wnt and Hedgehog and tumor-stroma exchanges play a critical role in the self-renewal and differentiation of cancer stem cells in breast cancer...
December 5, 2018: International Journal of Biochemistry & Cell Biology
Keiichi Takahashi
Introduction: Pleomorphic adenoma (PA) rarely originates in the mammary gland. This tumor is a benign mixed tumor and is commonly found in the salivary glands, but rarely shows findings similar to those of breast cancer. The tumor is misdiagnosed in 30-50% of the patients, including overdiagnosis of malignancy preoperatively, leading to unnecessary surgery for breast cancer. Case presentation: The present patient was a 45-year-old woman who exhibited no subjective symptoms...
December 2018: Annals of Medicine and Surgery
Ying Wang, Jia-Ning Chen, LinBin Yang, Jiaqian Li, Wei Wu, Min Huang, Ling Lin, Shicheng Su
PURPOSE: The different prognostic values of tumor-infiltrating neutrophils (TINs) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism. EXPERIMENTAL DESIGN: We evaluated CD66b+ neutrophils in primary tumors from 341 breast cancer patients from Sun Yat-Sen Memorial Hospital by immunohistochemistry. The association between stromal and parenchymal neutrophil counts and clinical outcomes was assessed in training set (170 samples), validated in internal validation set (171 samples), and further confirmed in external validation set (105 samples)...
November 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huan Cao, Melissa Kao Hui Lee, Haibo Yang, Siu Kwan Sze, Nguan Soon Tan, Chor Yong Tay
Tumor stromal residing cancer-associated fibroblasts (CAFs) are significant accomplices in the growth and development of malignant neoplasm. As cancer progresses, the stroma undergoes a dramatic remodeling and stiffening of its extracellular matrix (ECM). However, exactly how these biomechanical changes influence CAF behavior and the functional paracrine crosstalk with the neighboring tumor cells in a 3-dimensional (3D) microenvironment remains elusive. Herein, a collagen and alginate interpenetrating network (CoAl-IPN) hydrogel system was employed as a 3D in vitro surrogate of the cancerous breast tissue stromal niche...
November 27, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Jörg Kriegsmann, Mark Kriegsmann, Katharina Kriegsmann, Rémi Longuespée, Sören-Oliver Deininger, Rita Casadonte
PURPOSE: To present matrix-assisted laser desorption/ionization (MALDI) imaging as a powerful method to highlight various tissue compartments. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) tissue of a uterine cervix, a pancreas, a duodenum, a teratoma, and a breast cancer tissue microarray (TMA) are analyzed by MALDI imaging and by immunohistochemistry (IHC). Peptide images are visualized and analyzed using FlexImaging and SCiLS Lab software. Different histological compartments are compared by hierarchical cluster analysis...
November 24, 2018: Proteomics. Clinical Applications
Alison E Obr, Sushil Kumar, Yun-Juan Chang, Joseph J Bulatowicz, Betsy J Barnes, Raymond B Birge, Deborah A Lazzarino, Emily Gallagher, Derek LeRoith, Teresa L Wood
BACKGROUND: Early analyses of human breast cancer identified high expression of the insulin-like growth factor type 1 receptor (IGF-1R) correlated with hormone receptor positive breast cancer and associated with a favorable prognosis, whereas low expression of IGF-1R correlated with triple negative breast cancer (TNBC). We previously demonstrated that the IGF-1R acts as a tumor and metastasis suppressor in the Wnt1 mouse model of TNBC. The mechanisms for how reduced IGF-1R contributes to TNBC phenotypes is unknown...
November 20, 2018: Breast Cancer Research: BCR
Mieke Van Bockstal, Kathleen Lambein, Ann Smeets, Laurence Slembrouck, Patrick Neven, Ines Nevelsteen, Caroline Weltens, Erik Van Limbergen, Marie-Rose Christiaens, Chantal Van Ongeval, Hans Wildiers, Louis Libbrecht, Giuseppe Floris
BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of non-obligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence. In the present study, we investigated the prognostic potential of stromal characteristics. METHODS: Hematoxylin and eosin stained slides from 211 DCIS patients were reviewed...
November 12, 2018: European Journal of Surgical Oncology
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