Full length and delta lactoferrin display differential cell localization dynamics, but do not act as tumor markers or significantly affect the expression of other genes.

Lactoferrin is a secreted protein related to transferrin. Lactoferrin indirectly protects host cells against foreign insults by killing bacteria, scavenging free iron, and binding to receptors required for viral invasion. However, lactoferrin is also proposed to act directly on cells as a transcription factor and tumor suppressor gene. In addition to full length lactoferrin, a truncated form, called delta lactoferrin, can also be produced by alternative splicing. We show here that transformed and nontransformed cells are equally able to express both full length and delta lactoferrin. Moreover, both forms of lactoferrin failed to substantially modulate the expression of other genes. Thus, lactoferrin does not seem to directly control gene expression or inhibit tumor cell growth.

Normal cells control the growth of neighboring transformed cells independent of gap junctional communication and SRC activity.

The growth of many types of cancer cells can be controlled by surrounding normal cells. However, mechanisms underlying this phenomenon have not been defined. We used a layered culture system to investigate how nontransformed cells suppress the growth of neighboring transformed cells. Direct physical contact between transformed and nontransformed cells was required for growth suppression of transformed cells in this system; communication by diffusible factors was not sufficient. However, significant gap junctional communication was not required, indicating that other intercellular junctions mediated this growth regulatory response. We also report that the Src kinase activity in transformed cells was not directly inhibited by contact with nontransformed cells. Instead, nontransformed cells increased the expression of serum deprivation-response protein and the transcription factor four and a half LIM domain 1 in tumor cells. In addition, these results suggest mechanisms by which normal cells may block Wnt signaling, inhibit insulin-like growth factor activity, and promote host recognition of neighboring tumor cells.

Cancer screening literature in the period 2000-2002: pointers to future research avenues.

In order to determine which areas of cancer screening are currently receiving greatest emphasis in different parts of the world a Medline search of the literature for the period 2000-2002 was performed, concentrating attention on research into all aspects of efforts for early detection of tumours, with especial attention to methodology, motivation (including awareness of utility in the general populace and in minority groups), and intervention (professional training and general education). Focus on the skin, lung, cervix, breast, ovary + endometrium, oral cavity-oesophagus, gastric, colorectal, kidney + urinary tract and prostate, demonstrated large numbers of journals to be publishing papers in the field, with 10, 33, 130, 53, 24, 21, 6, 81, 12 and 58, respectively, in the period investigated, the grand total being 259. The average numbers of papers/journal ranged from 1.0-2.4 with only 15-35% appearing in journals with wide coverage. With the exception of oral, oesophageal and gastric cancer screening, an approximately 50% contribution in all areas was made by scientists in the US, followed by Europe (31% overall,) Asia (11%) then Australasia, Central and South America and Africa (3%, 2% and 1%, respectively). Clear differences were evident with the organ regarding specific topics receiving attention, most publications concerning the lung, ovary and urological tract dealing with detection methods. With the cervix and colorectum this topic accounted for half of the papers with especial attention to the relative advantages of the PAP smear, HPV testing and direct visual acetic acid (DVA) in the one, and FOBT and endoscopy in the other. Another major focus was found to be minority attitudes to breast, prostate and cervical screening in the US, whereas only few papers were found dealing with practical intervention, targeting professionals or screenees to increase participation in screening programs. The present approach suggested a number of areas requiring more attention, not least being the need for more comprehensive reviews across organs to allow the general reader a better understanding of the overall picture, and which avenues might best reward exploration in the future.