Macrophages promote the progression of premalignant mammary lesions to invasive cancer

Carron, Emily; Homra, Samuel; Rosenberg, Jillian; Coffelt, Seth B.; Kittrell, Frances; Zhang, Yiqun; Creighton, Chad J.; Fuqua, Suzanne A.W.; Medina, Daniel; Machado, Heather L.

doi:10.18632/oncotarget.14913

Cited by 65 publications

(73 citation statements)

References 51 publications

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“…Still, numerous studies have demonstrated that once infiltrated into the tumor microenvironment, TAMs generally play a protumoral role (37)(38)(39). Recently, Carron et al utilized a transplantable p53-null model of early progression to characterize immune cells in early-stage lesions (40). Macrophages were recruited to ductal hyperplasia, and the percentage of macrophages increased as the premalignant mammary lesions progressed to palpable tumors, suggesting a tumor-promoting role.…”

Section: Discussionmentioning

confidence: 99%

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine‐19 MRI cell tracking

Makela

Foster

2018

Magnetic Resonance in Med

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This study shows for the first time proof of the ability to use MRI cell tracking to visualize MAMs in the lungs. The ability to detect and monitor the number of TAMs in individual tumors with F MRI would allow for identification of breast tumors with heavy infiltration of TAMs and could be used as a biomarker for decisions about how to best treat these patients as well as for monitoring responses to therapy. Magn Reson Med 80:1138-1147, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

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Section: Discussionmentioning

confidence: 99%

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine‐19 MRI cell tracking

Makela

Foster

2018

Magnetic Resonance in Med

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“…Protumor TAMs were required for primary invasive mammary tumor formation in a transplantable p53-null mouse model studied for early progression [39]. Targeting TAMs with either selective monocyte targeting chemotherapeutic agent trabectedin, or CSF1 inhibitors, decreased TAM infiltration, reduced tumor growth and metastasis formation, while prolonging survival in a breast cancer xenograft mouse model [40,41].…”

Section: Tumor Growthmentioning

confidence: 99%

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

Qiu

Waaijer

Zwager

et al. 2018

Cancer Treatment Reviews

356

287

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Tumor-associated macrophages (TAMs) are important tumor-promoting cells in the breast tumor microenvironment. Preclinically TAMs stimulate breast tumor progression, including tumor cell growth, invasion and metastasis. TAMs also induce resistance to multiple types of treatment in breast cancer models. The underlying mechanisms include: induction and maintenance of tumor-promoting phenotype in TAMs, inhibition of CD8+ T cell function, degradation of extracellular matrix, stimulation of angiogenesis and inhibition of phagocytosis. Several studies reported that high TAM infiltration of breast tumors is correlated with a worse patient prognosis. Based on these findings, macrophage-targeted treatment strategies have been developed and are currently being evaluated in clinical breast cancer trials. These strategies include: inhibition of macrophage recruitment, repolarization of TAMs to an antitumor phenotype, and enhancement of macrophage-mediated tumor cell killing or phagocytosis. This review summarizes the functional aspects of TAMs and the rationale and current evidence for TAMs as a therapeutic target in breast cancer.

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“…Collagen plays a role in cell growth and tumor invasion in a cyclooxygenase 2 (COX2)dependent manner [40][41][42][43] as well as through overexpression of PAPP-A and activation of the DDR2/Snail axis [44]. In addition, the ECM and lymphatic vasculature are involved in immune cell recruitment and activation, and in the functioning of the immune system, to create a tumoral niche during involution (Figure 1) [45][46][47][48].…”

Section: Pregnancy-induced Breast Cancer Riskmentioning

confidence: 99%

Pregnancy and Breast Cancer: Pathways to Understand Risk and Prevention

Slepicka

Cyrill

Santos

2019

Trends in Molecular Medicine

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Several studies have made strong efforts to understand how age and parity modulate the risk of breast cancer. A holistic understanding of the dynamic regulation of the morphological, cellular, and molecular milieu of the mammary gland offers insights into the drivers of breast cancer development as well as into potential prophylactic interventions, the latter being a longstanding ambition of the research and clinical community aspiring to eradicate the disease. In this review we discuss mechanisms that react to pregnancy signals, and we delineate the nuances of pregnancyassociated dynamism that contribute towards either breast cancer development or prevention. Further definition of the molecular basis of parity and breast cancer risk may allow the elaboration of tools to predict and survey those who are at risk of breast cancer development. Parity: A Perspective for Therapeutic and Prophylactic InterventionBreast cancer is the most frequently diagnosed malignance in women. It strikes >1.6 million women worldwide, and about one in eight 8 women in the USA will develop breast cancer in their lifetime (Box 1 and Table 1). Most breast cancers arise because of dysfunction of cells in mammary ducts (50-70% of tumors) or lobules (10-15% of breast cancers), which categorizes these tumors as carcinomas, specifically adenocarcinomas. Some breast tumors are sarcomas, originating in the stroma or muscle. Other types and subtypes of breast cancer are less frequent, and a single diagnosis of breast cancer may refer to a combination of different tumors (www.breastcancer.org) (Box 1).Parity is known to have a dual effect on breast cancer risk. In many ways, breast tumorigenesis mimics several mechanisms that are commonly activated during pregnancy, including augmented cell proliferation, alterations in cell shedding, reduced cell apoptosis, altered gene expression, and extracellular matrix (ECM) modifications. On the other hand, epidemiological studies have provided evidence of the cancer-preventive benefits of pregnancy wherein an early age of pregnancy decreases the risk of breast cancer development. Although understanding the molecular mechanisms underlying these phenomena is still in its infancy, their elucidation will open new avenues to target breast cancer. Mammary Gland Composition and DevelopmentThe mammary gland is a complex and highly adaptive organ whose main function, in female mammals, is to produce milk during lactation for the sustenance of young offspring. The gland is composed of a variety of cell types, including fibroblasts, adipocytes, epithelial, endothelial, and immune cells. The epithelial cells can be further subdivided into multiple cell types that, together, form the branching structure of the gland and constitute the secretory alveoli during lactation. Two main epithelial cell compartments can be distinguished in the mammary gland: the luminal compartment [the inner cell layer, localized between the lumen (see Glossary),and the basal compartment] and the basal compartment (the outer layer surrounding ...

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Macrophages promote the progression of premalignant mammary lesions to invasive cancer

Cited by 65 publications

References 51 publications

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine‐19 MRI cell tracking

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine‐19 MRI cell tracking

Tumor-associated macrophages in breast cancer: Innocent bystander or important player?

Pregnancy and Breast Cancer: Pathways to Understand Risk and Prevention

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