Alpha-Fetoprotein, Stem Cells and Cancer: How Study of the Production of Alpha-Fetoprotein during Chemical Hepatocarcinogenesis Led to Reaffirmation of the Stem Cell Theory of Cancer

Abstract

Identification of the cells in the liver that produce α-fetoprotein during development, in response to liver injury and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas. When the cellular changes in these processes were compared to that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue-determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as normal tissues: stem cells, transit-amplifying cells and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, antiangiogenesis and differentiation therapy) are directed against the cancer transit-amplifying cells. When these therapies are discontinued, the cancer reforms from the cancer stem cells. Therapy directed toward interruption of the cell signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of regrowth of the cancer.

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

“…Tumor cells synthesize fetal proteins because of the "dedifferentiation" of adult hepatocytes [16] . During fetal life, AFP is synthesized at first by the yolk sac, then by the liver.…”

Molecular events in hepatic preneoplasia: A review

“…the ability to self renew (Sell, 2009). They resist chemotherapy, persist and then the cancer stem cells reform the cancer (Sell, 2008). There is a parallel between HCC and the rodent oval cell response to the drug DDC, which induces tumor cell formation.…”

Polymorphisms in Genes of the De Novo Lipogenesis Pathway and Overall Survival of Hepatocellular Carcinoma Patients Undergoing Transarterial Chemoembolization

“…Pathologically, AFP is produced and released into the circulation when liver injured or HCC developed, and serum AFP level together with other clinical parameters is widely used as a biomarker for HCC diagnosis or prognosis prediction (Sell, 2008). In this study, we observed that SNP rs9912300 in ACLY gene and SNP rs11871275 in ACACA gene were significantly associated with overall survival of TACE treated HCC patients with lower AFP level and higher AFP level under dominant model, respectively.…”