Boston, Mass. – Pan­cre­atic cancer patients face the worst sur­vival rates com­pared to all other forms of human cancer as the dis­ease is nearly impos­sible to diag­nose at an early stage when suc­cessful treat­ments might be pos­sible. Owing to late stage diag­nosis, the remaining clin­ical options are lim­ited to chemother­a­peutic approaches involving the use of such drugs as gem­c­itabine and 5-​​fluorouracil (5-​​FU). The pop­ular chemother­a­peutic agents have pro­duced lim­ited clin­ical suc­cess and North­eastern Uni­ver­sity pro­fessor Robert B. Camp­bell wanted to know why. Camp­bell and his grad­uate stu­dent inves­ti­gated whether or not mucin over­ex­pressed on the sur­face of human pan­cre­atic tumor cells might act as a phys­ical bar­rier, lim­iting the drug’s effectiveness.

The article dis­cussing the exper­i­ment, titled “Mucin Impedes Cyto­toxic Effect of 5-​​FU against Growth of Human Pan­cre­atic Cancer Cells; Over­coming Cel­lular Bar­riers for Ther­a­peutic Gain” is pub­lished in this month’s issue of The British Journal of Cancer.

In order to improve treat­ment approaches, we must con­sider the biology of pan­cre­atic tumors at the mol­e­c­ular, cel­lular and phys­i­o­log­ical levels,” said Dr. Camp­bell, Assis­tant Pro­fessor of Phar­ma­ceu­tical Sci­ences at the Northeastern’s Bouvé Col­lege of Health Sci­ences. “Our exper­i­mental find­ings in this study sug­gest that mucin is in fact a cel­lular bar­rier lim­iting chemother­a­peutic action of 5-​​FU against human pan­cre­atic cancer cells, making 5-​​FU less effective.”

Normal epithe­lial cells are cov­ered with mucin. In can­cerous tumor cells, mucin is over­ex­pressed on the cell’s sur­face. Dr. Camp­bell and his Ph.D., stu­dent Mr. Ashish V. Kalra were probing the effects of a single mucin variety, called MUC1, which is present on the sur­face of both normal epithe­lial cells and pan­cre­atic tumor cells and is respon­sible for the over­abun­dance of mucin on the latter. In order to find out whether or not mucin influ­enced the intra­cel­lular uptake of 5-​​FU, the researchers used inhibitors to limit the amount of MUC1 and reduce the mucin gly­ca­tion mesh sur­rounding cells. Camp­bell and Kalra observed that the expo­sure to inhibitors did not harm the healthy phys­i­ology of cells, how­ever, the reduc­tion of mucin mesh on the tumor cells enhanced the cell killing effect of 5-​​FU.

The exact mech­a­nism is not known, but we spec­u­late that the inhi­bi­tion of mucin may reduce the mucin mesh,” said Kalra. The authors spec­u­late that “this reac­tion may facil­i­tate the dif­fu­sion of drugs across the com­pro­mised mucus layer, improve intra­cel­lular drug uptake and enhance the effects of chemother­a­peutic drugs, such as 5-​​FU.”

Camp­bell and Kalra sug­gest that inhibiting the mucin on the sur­face of pan­cre­atic tumor cells and there­fore lim­iting the bar­rier that stands in the way of the chemother­a­peutic agents, may also lead to the need for smaller amounts of drugs to get the same results. The researchers also say that inves­ti­ga­tions into the role of mucin during chemotherapy in pre­clin­ical models are nec­es­sary to better under­stand the clin­ical impli­ca­tions of their exper­i­mental findings.

For more infor­ma­tion on Dr. Campbell’s research, and for a copy of the article, please con­tact Renata Nyul at 617–373-7424 or at r.​nyul@​neu.​edu.

About North­eastern

Founded in 1898, North­eastern Uni­ver­sity is a pri­vate research uni­ver­sity located in the heart of Boston. North­eastern is a leader in inter­dis­ci­pli­nary research, urban engage­ment, and the inte­gra­tion of class­room learning with real-​​world expe­ri­ence. The university’s dis­tinc­tive coop­er­a­tive edu­ca­tion pro­gram, where stu­dents alter­nate semes­ters of full-​​time study with semes­ters of paid work in fields rel­e­vant to their pro­fes­sional inter­ests and major, is one of the largest and most inno­v­a­tive in the world. The Uni­ver­sity offers a com­pre­hen­sive range of under­grad­uate and grad­uate pro­grams leading to degrees through the doc­torate in six under­grad­uate col­leges, eight grad­uate schools, and two part-​​time divi­sions. For more infor­ma­tion, please visit www​.north​eastern​.edu.