Normal Esophagus

The squamous epithelium of the normal human esophagus follows a similar differentiation pattern compared to the normal epidermis except that different keratins are expressed.

To better understand homeostasis in the normal esophagus the lab is overexpressing growth factors and disrupt/activate receptorfunction in either fibroblasts or esophageal keratinocytes. This is done by embedding the stromal cells in a three-dimensional collagen matrix and exposing overlayed keratinocytes to air to allow multi-layer formation and differentiation. The lab tests the hypothesis that continuous activation of keratinocytes through the local production of growth factors can induce a transformed phenotype. The lab hypothesizes that the EGF and TGF-ß receptor systems are dominant for maintaining the homeostatic balance in the normal esophageal mucosa and their dysfunction is critical for tumor development and progression and that fibroblasts and endothelial cells are recruited during tumor progression from the bone marrow stem cell pool.


Noma, K., Smalley, K.S.M., Lioni, M., Naomoto, Y., Tanaka, N., El-Deiry, W., King, A.J., Nakagawa, H., Herlyn, M.: An essential role for stromal fibroblasts and transformating growth factors (TGF)-ß in esophageal squamous cell carcinoma-induced angiogenesis. Gastroenterology 134: 1981-1993, 2008. PMID18439605 (PMCID2562524)

Kalabis, J., Li, G., Fukunaga-Kalabis, M., Rustgi, A., Herlyn, M: Endothelin-3 stimulates survival of goblet cells in organotypic cultures of human colonic epithelium. Am. J Physiol - GI Liver Physiol., 295: G1182-1189, 2008 PMID18832450 (PMCID2604801)

Lioni, M., Noma, K, Snyder, A., Rustgi, A., Diehl, J.A. , Herlyn, M., Smalley, K.: Bortezomib-induced cellular stress via the p38 MAPK pathway leads to a DNA damage response and apoptosis in esophageal squamous cell carcinoma cells. Molec. Cancer Ther: 7: 2866-2875, 2008. PMID18790767

Kalabis, J., Oyama, K., Okawa, T., Nakagawa, H., Michaylira, C.Z., Stairs, D.B., Figueiredo, J.L., Mahmood, U., Diehl, J.A., Herlyn, M., Rustgi, A.K.: A sub-population of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J. Clin. Invest. 118: 3860-3869, 2008. PMID19005570 (PMCID2579884)

Basu, D., Nguyen, T-T., Montone, K.T., Zhang, G., Wang, L-P., Diehl, J.A., Rustgi, A. K. Lee, J.T., Weinstein, G.S., Herlyn, M.: Mesenchymal sub-populations within squamous cell carcinomas exhibiting chemoresistance and phenotypic plasticity. Oncogene 29: 4170-4182, 2010. PMID20498638