ARTICLE IN PRESS Acta histochemica 106 (2004) 327—330
www.elsevier.de/acthis
12th International Congress of Histochemistry and Cytochemistry, La Jolla, California, 24–28 July 2004
The International Federation of Societies for Histochemistry and Cytochemistry (IFSHC) organizes an International Congress every 4 years. This year the Congress was held on the campus of the University of California, San Diego (UCSD) in association with the Histochemical Society on the theme: ‘‘Cellular Interactions in Development and Disease’’. Southern California provides a superb location for a congress, with its ideal climate, exotic vegetation, spectacular landscapes, fabulous beaches, the Pacific, surfers, local wines and exceptional cuisine, not to mention the marvelous tourist attractions (Sea World, San Diego Zoo, the Medway aircraft carrier, Tijuana). Despite the distractions of the area, the campus setting and outstanding scientific program of the Congress ensured full attendance at the scientific meetings and added to its success. It was indeed fortunate that the IFSHC congress was held on the campus, as there were no hotel vacancies in the San Diego area. On the opening day of the Congress downtown San Diego was overrun with a comics convention (Com-Con) with over 80,000 enthusiastic science fiction addicts. It is incredible that so many people indulge in science fantasies, when just up the road in La Jolla the realities of modern science were unfolding and the spectacular microscopical images shown (even in five dimensions) surpassed much of the computerized wizardry of sci-fi films. The tone for the Congress was set with the opening keynote lecture of Roger Y. Tsien (San Diego, CA) on ‘‘Breeding molecules to spy on cells’’ in which he reviewed the many new genetically encoded tags and indicators that have been developed to reveal specific gene products and doi:10.1016/j.acthis.2004.08.001
biochemical processes in living cells and organisms. He demonstrated the wide range of fluorescent proteins derived from jellyfish and corals that now cover the entire visible spectrum and can be used to identify and track molecules in living cells or distinguish specific cellular processes. He showed the application of green versus red pulse-chase labeling of old versus new copies of the same protein and parallel transmission electron microscopy to demonstrate ultrastructural localization. Roger Tsien was awarded the prestigious David Glick award in recognition of his outstanding scientific contributions to histochemistry and cytochemistry. The new cell biology where cell behavior can be visualized in living animals was brilliantly demonstrated by Robert Hoffman (San Diego, CA), who presented the acta histochemica lecture. He showed the use of dual-color fluorescence imaging of red fluorescent protein (RFP)-expressing tumors transplanted in green fluorescent protein (GFP) — expressing transgenic mice. These models dramatically display details of tumor-stroma interactions such as in tumor-induced angiogenesis, tumorinfiltrating lymphocytes, stromal fibroblasts and macrophages. In addition, he showed simultaneous visualization in vivo of both RFP- and GFP-expressing cells and the capability to visualize and track stem cells in vivo. Dual-color cells expressing GFP in the nucleus and RFP in the cytoplasm now permit real-time visualization of nuclear-cytoplasm dynamics including cell-cycle events and apoptosis. This multiple-color labeling of cells in vivo provides considerable advantages in studying cell dynamics and processes, which up to now could only be studied in vitro. It was quite remarkable to see
ARTICLE IN PRESS 328 well-delineated fluorescent colon tumors in living nude mice and the spread of metastases or their retreat in response to anti-tumor treatment. This model can now be used to screen anti-cancer drugs to determine their efficacy in animal models. At the end of the lecture there was a dramatic display of living transgenic GFP nude mice glowing a brilliant fluorescent green under blue light excitation. This lecture sponsored by acta histochemica has been published in vol. 106:77–87, 2004. Cellular dynamics and real-time imaging were demonstrated in five dimensions by Peter Friedl (Wurzburg, Germany) in his remarkable lecture that was sponsored by Histochemistry and Cell Biology showing the power of dynamic bright-field, confocal and multiphoton microscopy to reconstruct molecular live cell dynamics in tumors and immune cells. Cell contacts with collagen fibers in 3D tissue culture models and mouse dermis were demonstrated with time-lapse confocal reflection and multiphoton second harmonic generation imaging, showing the traction and remodeling of matrix structures by cancer cells. We could see the cells changing shape to adapt to the restrictions of the tissue scaffolds. This must be the first time ever that proteolysis and physical migration mechanisms of invading cells have been visualized in such dynamic detail. We could follow cancer cells breaching pathways through the matrix jungle and changing shape to squeeze through openings, some of which they created. Such studies have profound implications in understanding how cancer cells escape, migrate and spread to new sites and also provide new insights into old questions concerning amoeboid cell movement and cellshape changes. It is clear that time-resolved 3D histochemistry in live cell and tissue models can now provide new dynamic approaches to pathology, cell movement, migration and invasion. The use of fluorescent markers for cellular labeling and dynamics has come a long way in recent years. The Pearse Prize Award of the Royal Microscopical Society in honor of the late A.G. Everson Pearse was presented to Osamu Shimomura (Woods Hole, MA) in recognition of his discoveries of aequorin and GFP, which are so widely used today in cell biology and intracellular signaling. Aequorin is used as a calcium indicator and GFP as a marker of proteins. Dr. Shimomura described how he began to study bioilluminescence in the jellyfish Aequorea in 1961, and the many years of hard work, helped by his family and friends, in collecting huge quantities of jellyfish, dissecting their luminescent organs, leading to the eventual isolation of the photoprotein, aequorin. He also described the events leading to the later discovery of the GFP
R. Coleman chromophore. To illustrate the effectiveness of GFP as a marker, he dramatically produced a small bottle containing pure GFP, which shone brilliantly and spectacularly in the darkened lecture hall. The Pearse Prize was a fitting tribute to one of the great pioneers of modern histochemistry. The Piet Van Duijn Lectureship of the Histochemical and Cytochemical Section of the Netherlands Society of Cell Biology was awarded to Anton K. Raap (Leiden, The Netherlands) for his contributions to cell biology and pathology. He reviewed ‘‘Genes and gene transcripts under the microscope’’ and the ability since the early 1980s to label nucleic acid sequences with fluorochromes, in situ hybridization, and FISH techniques and their role in modern cytogenetics. He explained how resolution has improved and techniques for the exploitation of signal amplification. Modern cytogenetics and pathology owe a great deal to the contributions of these remarkable diagnostic techniques to determine genetic disorders. One of the main areas of tumor pathological research involves study of angiogenesis and metastasis. Erkki Ruoslahti (San Diego, CA) reviewed ‘‘Vascular zipcodes’’ and their role in these processes. There is tremendous heterogeneity in vascular endothelium. He lectured on vascular targeting peptides in normal tissues and how tumor vasculature expresses elevated homing peptides (with reference to specific integrins and aminopeptidases) and explained how it is easier to identify homing peptides rather than their receptors. Future therapies will involve ‘‘nanomedicine’’ and the design of compounds or nanodevices to deliver therapeutic payloads on demand that can find their targets. One approach may be to use fluorescein-labeled magnetic particles and applying magnetic fields. Antonio Nanci (Montreal, Canada) in his lecture sponsored by the Journal of Histochemistry and Cytochemistry brought us up to date on ‘‘Calcified tissues and biomineralization’’. He described studies of the rat hemimandible as a model to study both collagen and non-collagen based calcified tissues using a variety of static and dynamic histological methodologies. He showed that ameloblasts are possibly the fastest biosynthesizing cells in the body (within 2 min after introducing a marker). It was somewhat surprising to learn that bone is believed to have initially developed as an attachment for teeth and scales. The role of histochemistry in modern pathology was vividly illustrated in a remarkable lecture by Jiang Gu (Beijin, China), who described ‘‘The molecular morphology of SARS’’. He presented a graphic lecture of the first major epidemic of the
ARTICLE IN PRESS 12th International Congress of Histochemistry and Cytochemistry 21st century and the pathogenesis of this deadly and highly infectious new disease. His lecture showed the extraordinary measures needed to prevent the spread of SARS and at the same time protect the pathologists performing the biopsies and post-mortem studies. His lecture showed the extreme conditions (and bravery) faced by the pathological teams dealing with an unknown highly virulent agent being isolated for long periods in a class 3 containment facility and the difficulties posed by dissection while wearing protective ‘‘spacesuits’’. The lecture showed that SARS affects the immune system and this explained why most of the deaths occurred in the very young or the elderly or in people with weakened immune systems. The symposia and workshops held during the Congress were outstanding, though parallel sessions required difficult decisions and selection. One outstanding workshop reviewed the use of quantum dots as novel probes for fluorescence microscopy (sponsored by Quantum Dot Corporation). This included applications of quantum dots in multiplexing fluorescence immunohistochemistry, FISH probes, signal amplification, bio-imaging and as a tool to follow dynamics of individual proteins in live cells. A further workshop reviewed applications of laser capture microdissection (LCM) (sponsored by Arcturus Biosciences). We learned about the role of LCM in genomics and proteomics, in embryonic development, and in pathological studies. The workshop was accompanied by a practical handson demonstration of the Arcturus LCM. Judging by the response of the audience, LCM is a powerful tool that is going to find its way into very many cell biology, histochemistry and pathology research and diagnostic laboratories in the coming years. At the previous ICHC in York, UK, Gary Coulton (London, UK) presented a visionary plenary lecture on the future after the genome is deciphered. What does it all mean and can we start reassembling the parts (molecules) and deal with functional genomics. He now approached the question of whether ‘‘Histochemistry is an ‘-omic’’’ and tried to explain how we do science with analogies to fishing expeditions and persistent dogmas in science. His lecture, with special reference to skeletal muscle adaptation, reflected the need for integrated analyses of complex biological processes. There is a need to identify new biomarkers for pathological changes. Dedicated Biomics Centers now have many new tools available making it possible to identify markers utilizing the new -omics (genomics, proteomics, transcriptomics and metalobomics). An exciting novel tool, layered expression scanning (LES), was described by Gallya Gannot (NIH,
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Bethesda) in her lecture on ‘‘Histoinformatics: intersection of histopathology and bioinformatics’’. LES integrates two-dimensional gels or histological sections with an ‘‘array’’ of sequentially arranged analysis membranes. The methodology should facilitate rapid multiplex protein expression analysis of tissue sections and improve understanding of disease processes and lead to improved diagnostic and therapeutic markers. The symposium on ‘‘Mast cell development and disease’’ organized by Constance Oliver (Sao Paulo, Brazil) was enlightening in reminding us of the complexities of mast cells and the large number of mediators they synthesize and release in allergic and inflammatory responses. Metachromatic staining of granules is not useful for identifying immature mast cells. However, these immature cells can be identified using specific antibodies, and it can be shown that they migrate as precursors from the bone marrow to peripheral sites. Ann M. Dvorak (Boston, MA), who has contributed more than anybody else to our understanding of the ultrastructure of mast cells in pathology, presented a wide-ranging review on ‘‘Human mast cells in health and disease’’. Her talk described the various types of degranulation (anaphylactic and piecemeal) and the role of granules in secretion and storage. In addition, she reviewed the role of the cytoplasmic lipid bodies in human mast cells. Whereas both mast cells and lipid bodies are reservoirs of cytokines, the lipid bodies also participate in eicosanoid metabolism (production of arachidonic acid). A symposium on ‘‘Visualizing proteolysis’’ organized by Ron van Noorden (Amsterdam, The Netherlands) dealt with the importance of visualizing specific enzymes and proteases in living cells and tissues using novel chromogenic and fluorogenic substrates. Enzyme cytochemical methods for metabolic mapping in living cells are now providing important insights into pathophysiological processes. It was a pleasure to see so many enthusiastic Young Histochemist Awardees and their excellently presented posters (the wonders of PowerPoint) in the area of the trade exhibition. One of the items that caught my eye in the trade exhibition was a tissue-arrayer (Chemicon), which allows simple preparation of wax blocks of multiple tissues. This is a great tool for histopathological research and determining proteomic profiles of tumors. It could also be useful in preparing student test slides in histology or pathology. One examination slide could suffice for the whole exam and display many different tissues or biopsies. Although this report has been selective and only mentioned a small sampling of the presentations, it
ARTICLE IN PRESS 330 was abundantly clear from the congress that both histochemistry and cytochemistry are enjoying a renaissance. The last few years have seen the widespread introduction of exceptional new tools and techniques for following intracellular markers (laser scanning confocal microscopes, dual-photon and multiphoton instruments, laser dissection, tissue arrays, new chromogens and fluorochromes, microwave antigen-retrieval, increased automation and standardization). The lectures provided an indication of what trends we can anticipate in the next 4 years: improved whole body imaging (macroimaging), real-time visualization of subcellular events in living cells, and image analysis. Histochemistry has an important role in the nanotechnology boom. La Jolla was a great location and we had a really memorable meeting. Overall, the congress was very enjoyable, both socially and scientifically. The Histochemical Society and the local organizers deserve our heartiest congratulations as everything went very smoothly. Unfortunately more than 20 Chinese scientists were unable to receive visas to enter the USA. Perhaps the only real disappointment was the relatively poor attendance (only about 400 registrants), which was much lower than anticipated. It is hard to explain the overall poor
R. Coleman attendance figures considering the outstanding location, facilities, speakers and publicity. Are we presenting the wrong image of histochemistry? How is it possible that Cell Biology and Pathology meetings (where everybody is using histochemical and imaging techniques) attract considerably more participants? Gdansk, Poland was selected as the site for the next international congress (ICHC 2008). We trust that it will prove as successful as the congress in San Diego and that histochemistry in its broadest sense will attract many more participants. It was somewhat ironic that the death of Francis Crick in San Diego was reported on the last day of the conference. Francis Crick (1916–2004), the codiscoverer of the structure of the DNA molecule, paved the way for much of our modern histochemistry and cytochemistry during the last halfcentury. Raymond Coleman Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel. E-mail address:
[email protected]