Obligation for cell line authentication: Appeal for concerted action

Abstract

Cell lines isolated from various human cancers are widely used to study the mechanisms of tumor development and as preclinical models for tumor diagnosis and therapy. This key role played by cell lines in basic and applied cancer research is often taken for granted, but the chronic problem of cell line crosscontamination as well as of altered function due to over-subculturing—first recognized for HeLa cells more than three decades ago—has now become a major issue. As stated in a recent editorial published in Nature 1 ‘‘many studies have found that 18 to 36% of cell lines contain misidentified cells,’’ data which have been confirmed by the major cell repositories. Despite several recent initiatives to correct this intolerable situation, such as the open letter from a panel of scientists led by Roland Nardone to the US Secretary of Health and Human Services in 2007 2 and several subsequently published research articles, reviews and letters all confirming the dilemma of a still growing use of cross-contaminated cell lines, little has changed in reality. Many papers are still being submitted to this and other journals using mis-identified cell lines and many authors seem to be unaware of the problem. This situation prompted the Editors of International Journal of Cancer (IJC) to take the initiative and to impose strict rules for papers submitted for publication in the IJC beginning with the year 2010. In our new Instructions for Authors we now require that ... ‘‘manuscripts dealing with established cell lines have to provide authentication of cells by DNA profiling using Short Tandem Repeats (STR).’’ This ‘‘simple solution (of) routine, cheap DNA profiling’’—as stated in the Nature editorial—can be conducted at each laboratory using commercially available kits and is provided as a service by most cell culture repositories at a reasonable cost (see respective link in the Instructions for Authors). One major prerequisite for a reliable and comparable DNA profiling according to Nature—: ‘‘an electronic database of authenticated DNA profiles’’—of known cell lines has now been established by a consortium, thanks to the initiative and persistent activity of Willy Dirks of the German Cell Bank (DSMZ). This consortium, including major cell banks, has compiled a reference database of more than 2,300 known cell lines that is accessible online and with which scientists can compare their own DNA profiling data for authenticating a given cell line (see Dirks et al. Letter to the Editor, this issue, and the respective link to the database). Moreover, due to the long-standing efforts of Ian Freshney, a pioneer in cell culture technology and advocate of cell line authentication, a list of already confirmed cross-contaminated and mis-identified cell lines with the relevant references has been compiled; this is also freely accessible (see Freshney, Letter to the Editor, this issue, and respective link in the letter and Instructions for Authors of IJC). With these tools authors can easily see whether the cell line they want to use is already ‘indexed’ as cross-contaminated or mis-identified before they start with further authentication procedures. Thus, a solid basis has now been established to eliminate mis-identified cell lines that have produced misleading results and wasted funding, provided the scientific community will accept this offer. One prerequisite for the general acceptance of such a regulation is a concerted action of scientific journal editors and funding agencies to reject all manuscripts and grant applications (based on cell line data) without proper cell line authentication. When we first published a Mini Review in IJC in January 2008, we had addressed a Letter to the Editors-in-Chief of several leading cancer and cell biology journals asking them to join us in this effort, but got little to no response. Therefore, we now reiterate our appeal to the Editors-in-Chief of all life science journals publishing manuscripts with data based on cell lines to require proper authentication of all cell lines. This same petition is also being extended to all granting organizations to accept only grant applications with authenticated cell lines. A letter to major granting agencies has been sent by the Editors of IJC also requesting them to allow additional funds for cell line authentication. Some journals have already included respective demands in their instructions and others have indicated their willingness to do so, but too little has actually happened. The Editors of IJC are convinced that the time is overripe now to take consequent, concerted action on the part of all life science journals and granting agencies and to take the chance to defeat this ‘‘chronic disease’’ in cell culture research.