Tumor microenvironment: What can effusions teach us?

Malignant effusions, which are composed of malignant pleural and peritoneal fluid, are an unusual manifestation of cancer and frequently portend a poor prognosis. Neoplastic cells that disseminate into cavities containing effusions are highly metastatic and possess a strong autonomous proliferative drive while concurrently being stimulatory of exudative effusions. Most effusions will respond to transient therapeutic intervention, including the obliteration of potential space via pleurodesis. Cure, however, is rare, thus making effusions a biologically, biochemically, and clinically important topic of study. The local microenvironment that supports malignant growth, invasion, and dissemination of the solid primary tumor into the vasculature is composed of activated stroma that includes scaffolding consisting of materials that promote the tumor function, and vascular structures to provide conduits for travel and nutrient delivery. Less is understood about the tumor‐cell microenvironment in malignant effusions. The fluid nature of such a microenvironment when compared with the solid primary tumor may have significant implications for disease dissemination and progression. Dissecting the signaling activity and components of such microenvironments will improve our understanding and ultimately our ability to provide better patient care. Diagn. Cytopathol. 2005;33:316–319. © 2005 Wiley‐Liss, Inc.

[1]  J. Whang‐Peng,et al.  An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer. , 2001, Lung cancer.

[2]  M. Fiegl,et al.  Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH) , 2004, British Journal of Cancer.

[3]  I. Vlachonikolis,et al.  Assaying of Tumor Necrosis Factor α, Complement Factors, and α-1-Antitrypsin in the Diagnosis of Malignant Serous Effusions , 2001 .

[4]  K. Arimura,et al.  Vascular endothelial growth factor and proinflammatory cytokines in pleural effusions. , 2002, Respiratory medicine.

[5]  Carlos López-Otín,et al.  Matrix metalloproteinases and tumor progression. , 2003, Advances in experimental medicine and biology.

[6]  L. Burgess Biochemical analysis of pleural, peritoneal and pericardial effusions. , 2004, Clinica chimica acta; international journal of clinical chemistry.

[7]  Richard W. Light,et al.  Transforming Growth Factor β Induces Vascular Endothelial Growth Factor Elaboration from Pleural Mesothelial Cells in Vivo and in Vitro , 2002 .

[8]  J. Nesland,et al.  Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): Co-expression in metastatic serous ovarian carcinoma , 2004, Clinical & Experimental Metastasis.

[9]  J. Nesland,et al.  Interleukin-8 and vascular endothelial growth factor mRNA and protein levels are down-regulated in ovarian carcinoma cells in serous effusions , 2004, Clinical & Experimental Metastasis.

[10]  L. Liotta,et al.  Tumor cell interactions with the extracellular matrix during invasion and metastasis. , 1993, Annual review of cell biology.

[11]  J. Folkman,et al.  ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESIS , 1971, The Journal of experimental medicine.

[12]  Y. Morishita,et al.  Lysophosphatidic Acid (LPA) in Malignant Ascites Stimulates Motility of Human Pancreatic Cancer Cells through LPA1* , 2004, Journal of Biological Chemistry.

[13]  B. Hemmerlein,et al.  Real-time reverse transcription-polymerase chain reaction assay for GA733-2 mRNA in the detection of metastatic carcinoma cells in serous effusions. , 2003, American journal of clinical pathology.

[14]  V. Antony,et al.  Pathophysiology of pleural space infections. , 1999, Seminars in respiratory infections.

[15]  W. Stetler-Stevenson,et al.  Proteases in invasion: matrix metalloproteinases. , 2001, Seminars in cancer biology.

[16]  G. Giannelli,et al.  Cancer Invasion: Watch Your Neighbourhood! , 2003, Tumori.

[17]  Y. Lee,et al.  Vascular endothelial growth factor: the key mediator in pleural effusion formation , 2002, Current opinion in pulmonary medicine.

[18]  N. Siafakas,et al.  Diagnostic value of interleukin-1alpha, interleukin-6, and tumor necrosis factor in pleural effusions. , 2002, Chest.

[19]  R. Whitehead,et al.  Tissue culture studies of malignant effusions. , 1975, British Journal of Cancer.

[20]  G. Mills,et al.  Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. , 2001, Journal of the National Cancer Institute.

[21]  Masao Tanaka,et al.  A possible role of TGF-β in the formation of malignant effusions , 1995 .

[22]  N. Kaneko,et al.  Clinical significance of vascular endothelial growth factor in patients with primary lung cancer , 2002, Respirology.

[23]  David A. Cheresh,et al.  Role of integrins in cell invasion and migration , 2002, Nature Reviews Cancer.

[24]  R. Light,et al.  Vascular endothelial growth factor level correlates with transforming growth factor-beta isoform levels in pleural effusions. , 2000, Chest.

[25]  S. Sone,et al.  Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer , 1999, Cancer Immunology, Immunotherapy.

[26]  S. Rodenhuis,et al.  Malignant effusions contain lysophosphatidic acid (LPA)-like activity. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  E. Kohn,et al.  Granulin‐epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma , 2004, Cancer.

[28]  A. van Dalen,et al.  Vascular endothelial growth factor (VEGF) concentration in sera and tumor effusions from patients with ovarian carcinoma. , 2004, Anticancer research.

[29]  Z. Darżynkiewicz,et al.  Relative abundance and patterns of correlation among six cytokines in pleural fluid measured by cytometric bead array. , 2003, International journal of molecular medicine.

[30]  L. Matrisian,et al.  Matrix metalloproteinases in tumor-host cell communication. , 2002, Differentiation; research in biological diversity.

[31]  G. Mills,et al.  The emerging role of lysophosphatidic acid in cancer , 2003, Nature Reviews Cancer.