ErbB receptor stimulation is required for mouse Colon adenoma organoids to form crypts

mice typically grow as spheroidal cysts and do not produce crypts. The adenoma organoids require EGF, but not Wnt, R-spondin or Noggin for continuous passaging. However, when mouse colon adenoma spheroids are grown for more than 10 days in the presence of EGF, crypt formation occurs. EGF, EREG, β-cellulin, Neuregulin-1 or AREG are sufficient for initiating crypt formation, however, neuregulin-1 is more potent than the other EGF-family members. EGFR and ErbB2 inhibitors both prevent crypt formation in these adenoma cultures. Either EGFR:ErbB2 or ErbB3:ErbB2 signaling is sufficient to initiate adenoma crypt budding and elongation. ErbB2 inhibitors may provide a therapeutic avenue for ablating colon adenomas.