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Potential Role for Activated Leukocyte Cell Adhesion Molecule and Neural Cadherin in Metastasis to the Lung Microcirculation* FREE TO VIEW

Judy King, MD, PhD; Solomon Ofori-Acquah, PhD; Troy Stevens, PhD; Abu-Bakr Al-Mehdi, MD, PhD
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*From the Center for Lung Biology, University of South Alabama, Mobile, AL.

Correspondence to: Judy A.C. King, MD, PhD, Associate Professor, Pathology and Pharmacology, Department of Pathology, University of South Alabama, 2451 Fillingim St, Mobile, AL 36617-2293; e-mail: jking@usouthal.edu

Chest. 2004;125(5_suppl):150S-151S. doi:10.1378/chest.125.5_suppl.150S
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Large pulmonary vessels are thought to develop by angiogenesis, while distal capillaries in the lung are thought to develop by vasculogenesis. Such distinct origins of the endothelium confer unique functional attributes, even in the adult.

Our laboratory has established cultures of pulmonary artery endothelial cells (PAECs) and pulmonary microvascular endothelial cells (MVECs) from adult rats, and have characterized them morphologically and biochemically. Several molecules are differentially expressed. Gene microarray data have demonstrated greater activated leukocyte cell adhesion molecule (ALCAM [CD166]) and neural (N)-cadherin expression in MVECs when compared to PAECs. ALCAM, a member of the Ig superfamily, serves as a ligand for the CD6 molecule and is involved in homophilic or heterophilic adhesion. The expression of ALCAM has been correlated with the progression and metastasis of melanoma. N-cadherin is a transmembrane glycoprotein that is involved in calcium-dependent cell-cell adhesion. N-cadherin has been associated with tumor invasion and metastatic disease. Immunofluorescence has revealed greater membrane staining for ALCAM in MVECs than in PAECs (cultured rat cells). Immunohistochemistry for N-cadherin in human and rat lung sections exhibited strong staining in large and intermediate-size vessels. Capillary endothelial cells occasionally exhibit staining that is less intense.

It has been proposed by other investigators that metastatic tumor preferentially goes to specific organs or parts of organs. Human lung carcinoma (ie, non-small cell carcinoma) is strongly positive for ALCAM (4+) and exhibits occasional staining for N-cadherin (0 to 1+). The human breast carcinoma cell line is positive for ALCAM by flow cytometry. Human breast carcinoma (tissue section) has strong immunohistochemical staining with ALCAM (3+ to 4+) and with N-cadherin (0 to 2+). These findings collectively suggest that ALCAM and/or N-cadherin may fulfill a role in the homing of metastatic carcinoma to the lung or, possibly, in the vascular proliferation that is associated with metastatic disease.

Abbreviations: ALCAM = activated leukocyte cell adhesion molecule; MVEC = microvascular endothelial cell; N = neural; PAEC = pulmonary artery endothelial cell




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