Human squamous carcinoma cells express complex defects in the control of proliferation and differentiation

Four human squamous carcinoma cell (SCC) lines (SCC-9, SCC-13, SCC-15, and SCC-25) were studied to characterize their relative ability to control proliferation and differentiation. These experiments were based on previous data that established that in normal human keratinocytes three distinct and sequential steps are involved in the integrated control of proliferation and differentiation: 1) reversible growth-arrest at a predifferentiation state, 2) irreversible loss of proliferative potential, and 3) terminal differentiation. The current results show that SCC can show changes in the culture conditions required to undergo reversible growth-arrest and SCC can express partial or complete defects in their ability to irreversibly growth-arrest or terminally differentiate. For example, SCC-9 and SCC-25 cannot irreversibly growth-arrest or terminally differentiate, SCC-13 can irreversibly growth-arrest but cannot terminally differentiate, and SCC-15 can irreversibly growth-arrest and terminally differentiate to a moderate extent. These results therefore extend previous data by establishing that the malignant transformation of human epithelial cells does not simply result from defects in the control of terminal differentiation but rather from a combination of complex defects in the regulation of proliferation and differentiation.