The microenvironment of the tumour-host interface
TL;DR: A new class of cancer therapies that targets this pathological communication interface between tumour cells and host cells is currently under development.
Abstract: Throughout the entire process of cancer aetiology, progression and metastasis, the microenvironment of the local host tissue can be an active participant. Invasion occurs within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate migration, and promote proliferation and survival. A new class of cancer therapies that targets this pathological communication interface between tumour cells and host cells is currently under development.
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TL;DR: Understanding of the origins and nature of cancer metastasis and the selection of traits that are advantageous to cancer cells is promoted.
3,863 citations
Cites background from "The microenvironment of the tumour-..."
...Growth-factor signaling, such as that mediated by HGF through the Met receptor, can modulate many of these activities either directly or indirectly (Liotta and Kohn, 2001)....
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TL;DR: It is the right time for medical societies and public health regulators to consider the causal role of human papillomavirus infections in cervical cancer and to define its preventive and clinical implications.
Abstract: The causal role of human papillomavirus infections in cervical cancer has been documented beyond reasonable doubt. The association is present in virtually all cervical cancer cases worldwide. It is the right time for medical societies and public health regulators to consider this evidence and to define its preventive and clinical implications. A comprehensive review of key studies and results is presented.
3,333 citations
TL;DR: The targets and mechanisms of M SC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches are discussed.
Abstract: Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues. They can differentiate into cells of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as well as cells of other embryonic lineages. MSCs can interact with cells of both the innate and adaptive immune systems, leading to the modulation of several effector functions. After in vivo administration, MSCs induce peripheral tolerance and migrate to injured tissues, where they can inhibit the release of pro-inflammatory cytokines and promote the survival of damaged cells. This Review discusses the targets and mechanisms of MSC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches.
3,142 citations
TL;DR: The most common human cancers — lung, breast and prostate — have a great avidity for bone, leading to painful and untreatable consequences.
Abstract: The most common human cancers --lung, breast and prostate -- have a great avidity for bone, leading to painful and untreatable consequences. What makes some cancers, but not others, metastasize to bone, and how do they alter its physiology? Some of the molecular mechanisms that are responsible have recently been identified, and provide new molecular targets for drug development.
2,367 citations
Cites background from "The microenvironment of the tumour-..."
...For example, systemically administered FGF-1 restores trabecular microarchitecture and increases bone volume (15)....
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...PTHrP (1-36) as a skeletal anabolic agent for the treatment of osteoporosis....
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TL;DR: Signs of an immune response within colorectal cancers are associated with the absence of pathological evidence of early metastatic invasion and with prolonged survival.
Abstract: Background The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown. Methods We studied pathological signs of early metastatic invasion (venous emboli and lymphatic and perineural invasion) in 959 specimens of resected colorectal cancer. The local immune response within the tumor was studied by flow cytometry (39 tumors), low-density-array real-time polymerase-chain-reaction assay (75 tumors), and tissue microarrays (415 tumors). Results Univariate analysis showed significant differences in disease-free and overall survival according to the presence or absence of histologic signs of early metastatic invasion (P<0.001). Multivariate Cox analysis showed that an early conventional pathological tumor–node–metastasis stage (P<0.001) and the absence of early metastatic invasion (P=0.04) were independently associated with increased survival. As compared with tumors with signs of early metastatic invasion, tumors without such signs had increased infiltrates of i...
1,956 citations
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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
28,811 citations
Additional excerpts
...gif" NDATA ITEM> ]> Neoplasia can be considered a pathological imbalance of tissue-cell societie...
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TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Abstract: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti-angiogenic molecules, some of which are already in clinical trials The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases But owing to several unanswered questions, caution is needed
8,561 citations
"The microenvironment of the tumour-..." refers background in this paper
...In response to trophic signals, vascular cells, wounded epithelial sheets or neurites will migrate, penetrate tissue barriers and establish appropriate new anastomose...
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TL;DR: It is reported that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases and their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis.
Abstract: Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.
5,132 citations
3,852 citations
TL;DR: General themes are emerging that yield new strategies for prognosis and therapy of hu- man metastatic cancer, and an imbalanced regulation of motility and proteoly- sis appears to be required for invasion and metastasis.
2,776 citations
"The microenvironment of the tumour-..." refers background in this paper
...Altered cell–cell and cell–substratum survival signals may release normal constraints, thereby enabling malignant cells to migrate across tissue boundarie...
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