Association of Macrophage Infiltration with Angiogenesis and Prognosis in Invasive Breast Carcinoma1 (original) (raw)
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma
Cancer research, 1996
Angiogenesis is a key process in tumor growth and metastasis and is a major independent prognostic factor in breast cancer. A range of cytokines stimulate the tumor neovasculature, and tumor-associated macrophages have been shown recently to produce several important angiogenic factors. We have quantified macrophage infiltration using Chalkley count morphometry in a series of invasive breast carcinomas to investigate the relationship between tumor-associated macrophage infiltration and tumor angiogenesis, and prognosis. There was a significant positive correlation between high vascular grade and increased macrophage index (P = 0.03), and a strong relationship was observed between increased macrophage counts and reduced relapse-free survival (P = 0.006) and reduced overall survival (P = 0.004) as an independent prognostic variable. These data indicate a role for macrophages in angiogenesis and prognosis in breast cancer and that this cell type may represent an important target for im...
Tumour-associated macrophages in breast cancer and their prognostic correlations
The Breast, 1998
S U M M A R Y. Breast cancer is known as a macrophage (Mps) infiltrated type of tumour. The biological and prognostic significance of this phenomenon is not clear. The intensity of intratumoural Mps infiltration as well as its correlation with reliable prognostic parameters has been studied. The extent of Mps infiltration was evaluated by immunohistochemistry in paraffin-embedded sections from formalin-fixed samples of 34 node-negative and 86 node-positive primary breast cancers using KP-1 (CD-68) DAK0 monoclonal antibody (MoAB) and polyclonal antibody to lysozyme. Intensive Mps infiltration was closely associated with absence of regional metastases: 16 (47%) node-negative and only 5 (5.8%) node-positive tumours were infiltrated intensively (more than 500 IQ-l+ cells in 40 high-power fields). However, when stratified into subgroups, intensity of Mps infiltration was strongly associated with prognostic parameters, which are traditionally considered to be the signs of bad prognosis (high tumour grade, oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and high mitotic rate).
Macrophages Regulate the Angiogenic Switch in a Mouse Model of Breast Cancer
The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy. (Cancer Res 2006; 66(23): 11238-46)
Human pathology, 2017
Tumor associated macrophages (TAM) resemble M2 macrophages, promote tumor invasion and show strong expression of CD163 in breast cancer. We here investigated the association between CD163 positive macrophages and vascular invasion, molecular subgroups, mode of detection, and patient outcome. We performed a population-based, retrospective study of invasive breast cancer from the Norwegian Breast Cancer Screening Programme in Vestfold County (2004-2009), including 200 screen-detected and 82 interval cancers. Immunohistochemically CD163 positive macrophages were counted in the most active areas (hot-spots) and dichotomized as high (upper quartile) and low counts. Lymphatic vessel involvement (LVI) and blood vessel invasion (BVI) were recorded separately based on immunohistochemical staining (D2-40 and CD31 antibodies). High levels of CD163 positive macrophages were associated with blood vessel invasion and lymphatic involvement as well as interval cancer detection when compared to scre...
British journal of cancer, 1999
Necrosis is a common feature of invasive carcinoma of the breast and is caused by chronic ischaemia leading to infarction. Although necrosis was previously assumed to be due to a generally poor blood supply in the tumour, in this study we show that it is present in tumours with focal areas of high vascular density situated away from the actual sites of necrosis. This may account, in part, for the previous observation that necrosis is linked to poor prognosis in this disease. Highly angiogenic tumours often display blood vessel shunting from one tumour area to another, which further exacerbates ischaemia and the formation of tumour necrosis. We have recently demonstrated that high focal microphage infiltration into breast tumours is significantly associated with increased tumour angiogenesis and poor prognosis and that the macrophages accumulate in poorly vascularized, hypoxic areas within breast tumours. In order to investigate the interactions of macrophages with chronic ischaemia ...
Dual role of macrophages in tumor growth and angiogenesis
Journal of Leukocyte Biology, 2006
During the neoplastic progression, macrophages as well as dendritic and NK cells are attracted into the tumor site and initiate the immune response against transformed cells. They activate and present tumor antigens to T cells, which are then activated to kill tumor cells. However, tumor cells are often capable of escaping the immune machinery. As the immune surveillance is not sufficient anymore, tumor-associated macrophages contribute to tumor progression. It is notable that tumor-associated macrophages promote the proliferation of tumor cells directly by secreting growth factors. They also participate in tumor progression by acting on endothelial cells and thus promoting the neovascularization of the tumor. Tumor-associated macrophages are indeed key protagonists during angiogenesis and promote each step of the angiogenesis cascade.
Tumor-associated macrophages in breast cancer
Journal of mammary gland biology and neoplasia, 2002
Neoplastic cells form only one part of a complex network of cell types that make up a breast tumor. The normal cell types that make up the nonneoplastic components of tumors include fibroblasts, endothelium, and inflammatory cells, such as tumor associated macrophages (TAMs). TAMs have the potential to carry out both anti- and protumor activities In their antitumor role TAMs can present tumor antigens to cytotoxic T-cells and are capable of being directly cytotoxic to neoplastic cells. Conversely, TAMs are also able to promote tumor growth directly by secreting breast tumor mitogens, such as epidermal growth factor, and indirectly by stimulating tumor angiogenesis and metastasis. Recent studies have indicated that in breast cancers the protumor role of TAMs is dominant, and that TAMs may be executing a "wound healing" type of process in response to stimuli found in the tumor microenvironment, such as hypoxia. As such, TAMs may provide opportunities for future therapeutic i...
Tumor-Associated Macrophage: Its Role in Tumor Angiogenesis
2006
Macrophages are important cells in wound healing, providing aids for tissue cell growth, tissue matrix remodeling and angiogenesis. Solid tumor comprises not only tumor cells, but also tissue matrix and many stromal cells such as fibroblasts and macrophages. Accumulating research results have suggested tumor-associated macrophages (TAMs) functioning in tumor cell proliferation, tumor cell migration and invasion, and tumor angiogenesis. In this review article, we review data from clinical investigations and animal studies to demonstrate the association of TAMs with tumor angiogenesis. We also discuss results of several mechanistic studies to provide pos- sible mechanisms for TAMs-associated angiogenesis. By interacting with cancer cells, TAMs can be induced to express more cytokines and tissue matrix-degrading enzymes, such as matrix metalloproteinases, plasminogen activators and cathepsin B, that are either direct angiogenic factors or tissue matrix modulators responsible for promot...
Cancer Science, 2007
The focus of the present study was whether and how infiltrating macrophages play a role in angiogenesis and the growth of cancer cells in response to the inflammatory cytokine interleukin (IL)-1β β β β. Lewis lung carcinoma cells overexpressing IL-1β β β β grew faster and induced greater neovascularization than a low IL-1β β β β-expressing counterpart in vivo. When macrophages were depleted using clodronate liposomes, both neovascularization and tumor growth were reduced in the IL-1β β β β-expressing tumors. Co-cultivation of IL-1β β β βexpressing cancer cells with macrophages synergistically augmented neovascularization and the migration of vascular endothelial cells. In these co-cultures, production of the angiogenic factors vascular endothelial growth factor-A and IL-8, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 were increased markedly. The production of these factors, induced by IL-1β β β β-stimulated lung cancer cells, was blocked by a nuclear factor (NF)-κ κ κ κB inhibitor, and also by the knockdown of p65 (NF-κ κ κ κB) and c-Jun using small interference RNA, suggesting involvement of the transcription factors NF-κ κ κ κB and AP-1. These results demonstrated that macrophages recruited into tumors by monocyte chemoattractant protein-1 and other chemokines could play a critical role in promoting tumor growth and angiogenesis, through interactions with cancer cells mediated by inflammatory stimuli. (Cancer Sci 2007; 98: 2009-2018)