Article Text

Distribution and mRNA Expression of Insulin-Like Growth Factor System in Pulmonary Lymphangioleiomyomatosis
  1. Julio C. Valencia,
  2. Kazuhiro Matsui,
  3. Carolyn Bondy,
  4. Jian Zhou,
  5. Audrey Rasmussen,
  6. Kevin Cullen,
  7. Zu-Xi Yu,
  8. Joel Moss,
  9. Victor J. Ferrans
  1. 1From the Pathology Section (J.C.V., K.M., Z-X.Y., V.J.F.), National Heart, Lung, and Blood InstituteBethesda, Md
  2. 2Pulmonary Critical Care Medicine Branch (J.M.), National Heart, Lung, and Blood Institute, Bethesda, Md
  3. 3Developmental Endocrinology Branch (C.B., J.Z.), National Institute of Child Health and Development, National Institutes of Health, Bethesda, Md,
  4. 4Lombardi Cancer Research Center (A.R., K.C.), Georgetown University Medical Center, Washington, DC.
  1. Address correspondence to: Victor J. Ferrans, MD, PhD, National Institutes of Health, National Heart, Lung, and Blood Institute, Bldg. 10/2N240, 10 Center Drive, MSC-1518, Bethesda, MD 20892-1518. E-mail vf10e{at}


Background Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors.

Methods To evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients.

Results IGF-1, IGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells.

Conclusions These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells.

  • pulmonary pathology
  • lymphangioleiomyomatosis
  • immunohistochemistry
  • insulin-like growth factors
  • lung disease

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